Many returns to Casa Martini: Guido has returned from his experience in Africa, Lele returns with his twins. Cettina and her family are absent: the Martini family's former housekeeper has apparently disappeared in a shipwreck.
A nasty surprise awaits Guido and Maria: they discover that their apartment's tenant refuses to return the keys. During a chat, Grandpa Libero reveals to Lele that he's feeling the weight of old age.
With Grandpa Libero gone, Lele is left to care for the entire family. Elena and Bobò are anxious about their first day of school. Annuccia continues to behave rather arrogantly toward her younger siblings.
Maria is assigned the case of a little girl hospitalized for stomach pains, likely due to her grandfather's absence, who has gone on a long trip. Maria discovers that the truth is much more painful.
Fanny and Maria become friends, but Maria is jealous because she fears Fanny is courting Guido. She doesn't suspect that her young colleague is interested in another member of her family: her father.
Maria's pregnancy progresses, and so do the cravings. Meanwhile, a child neuropsychiatry department will be opened at the clinic, which is precisely the young doctor's specialty.
Libero and Enrica return from Puglia for the Christmas holidays. Meanwhile, Guido resists the idea of starting a relationship with his newly reunited mother. Fanny discovers toxic waste dumped in a river.
Guido and Ave have a tough confrontation, and Ave increasingly feels the pain of not being there when they needed her. Giulio wins the lottery, and an unexpected snowfall in Poggiofiorito brightens Christmas Day.
Maria prepares an exclusive evening for herself and Guido, who is forced to stand her up. She's felt a bit left out of Guido's life since she's expecting a baby, and she's convinced he no longer likes her since she's pregnant.
As Maria's final months of pregnancy approach, Lele senses that becoming a grandfather will be a new adventure, completely different from being a father. Especially since Maria's water breaks early!
Grandpa Libero returns to Rome to meet little Paola. Lele tries to convince Fanny not to continue the relationship, but she's truly in love.
Giulio convinces Grandpa Libero to participate in a new program, Cambio Nonno (Grandpa Change). Libero accepts and finds himself with a new family, one from Lazio, to boot. Consequently, the grandfather of that family goes to live with the Martinis.
The twins notice the silhouette of a woman behind the window of the Torello house and believe it to be Cettina's ghost. Grandma Enrica, with her friends, organizes a séance to summon her.
A friend of Annuccia's surprises Fanny and Lele. Annuccia, after finding out from her friend, is reluctant to accept her father's new girlfriend, unlike the rest of the family, who are still somewhat confused.
A colleague confesses to Lele that he's in love with Fanny. Lele, embarrassed, doesn't reveal his relationship with the girl. Meanwhile, Ave tells Guido that his sister hasn't taken the news of having a brother well.
The twins convince Bianca and Lele to go to the water park, where they hope to make them fall in love. Fanny decides to tag along to get to know the twins, but they're having a hard time.
Fanny decides to introduce Lele to her family. Ave receives permission from the Martinis to move into their home, as the housekeeper Melina is unable to care for the baby alone.
Bianca receives a commission from the Vatican to make a chocolate sculpture, but the twins smash it to pieces. Lele helps Bianca, and after working all night, the two kiss.
Lele discovers that Fanny's tests were switched, meaning she isn't pregnant. The two decide to break up, and Lele can now live with Bianca, but Bianca is about to return to the Netherlands.
The Martini family is summoned by the police because an American woman is asking for them. The Martinis discover that the woman is actually Cettina, although she seems to remember nothing of her past.
Lele tries, in vain, to reconnect with Bianca, who is hurt by the doctor's treatment. She felt seduced and abandoned because of Fanny's pregnancy, and it's difficult to forgive.
Maria believes Guido is cheating on her with Albina, unaware that she is his sister. Lele makes one last attempt to win Bianca back, but it's too late: she must leave for the Netherlands.
The Martini family organizes a surprise birthday party for Lele, who is desperate for the woman he loves. Ciccio learns that Tracy has returned to Rome. He can't resist: he goes to visit her at the riding stables!
Guido confesses his betrayal to his wife, who packs her bags and goes to live alone with her daughter, driving Guido into despair. Ciccio realizes he's in love with Tracy. Meanwhile, Lele goes to London and declares his love for Bianca.
Guido tries to win Maria back, but when she seems to have forgiven him, she sends him a request for separation. Lele intends to stay in Rome forever and announces this to his family, who are thrilled.
Grandpa Libero and Ciccio's double wedding is approaching, and preparations are in full swing. Maria and Guido must meet with their lawyer for a preliminary meeting to discuss the separation. But will it be the right choice?