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A 42‐year‐old female with a personal history of Grade II infiltrating ductal breast carcinoma, treated under surgical procedure in 2018, whose hormonal profile included estrogen, progesteronic and HER‐2 positive receptors, and a Ki67 proliferative index (20–25%), was referred to our dermatological outpatient clinic complaining worsening of her chronic spontaneous urticaria. The patient was under treatment with etuximide, exemestane, anastrozole, and trastuzumab. Our patient reported intermittent episodes of hives of 8 years of evolution with good control with second‐generation antihistamines. However, in the past year, the intensity and frequency of the outbreaks was increased with the development of angioedema until completing 23 consultations through the emergency department being treated in all of the episodes with short cycles of oral corticosteroids. This case reported is particularly complex due to different points that we develop below: (a) oncological patient as special population; (b) differential diagnosis with other forms of urticaria such as vasculitis urticaria, inducible urticaria, and autoimmune progesterone dermatitis; (c) spontaneous chronic urticaria of difficult control at labeled dose of omalizumab; (d) concomitant treatment with another biological drug.