Antibody-drug conjugates (ADCs) offer new options for precision tumor therapy with potent cytotoxic load. In breast cancer, despite their efficacy, their application is not without adverse events. Oral stomatitis is a frequent, dose-limiting toxicity. The associated symptoms, mainly oral pain, can affect the patient's quality of life and lead to a delay and reduction of the dose or to discontinuation of treatment. Datopotamab-Deruxtecan (Dato-DXd) is an ADC targeting TROP-2. Stomatitis is the most frequent adverse effect associated with this drug. The TROPION-PanTumor01 and BEGONIA trials revealed rates of 50-70% for any grade of stomatitis and 10-15% for grade ≥3 events. Trop-2, in its normal form, is expressed in the lining of the mucosa and salivary glands. Dato-DXd targets these cells. Damage can manifest as erythema, ulceration, oropharyngeal pain, and mucosal bleeding. Other possible clinical presentations include xerostomia, gingival edema, dysphagia, and dysgeusia. Appropriate management involves three stages: prevention, monitoring, and timely treatment. Preventive recommendations include education, a basic oral care plan, and the use of a steroid mouthwash. Oral cryotherapy during Dato-DXd infusions should also be considered. Monitoring by a specialized dentist allows us to support the patient, reinforce the instructions, and treat in a timely manner. Supportive care includes frequent use of gentle mouthwash and administration of oral solutions containing steroids. Specialized nutritional support and adequate pain management are recommended. Dose reductions for grade 2 to 3 stomatitis should be considered. These recommendations provide clinicians with a multidisciplinary approach to managing this toxicity.

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