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Drug hypersensitivity reactions to essential antibiotics like vancomycin pose significant diagnostic and therapeutic challenges, particularly in vulnerable populations such as pediatric patients with immune deficiencies. We present the case of a 7-year-old girl with primary immunodeficiency who experienced immediate hypersensitivity reactions to vancomycin, including urticaria and angioedema, managed with corticoids and antihistamines. The Basophil Activation Test (BAT) conducted two years after the last allergic episode revealed significant basophil activation across all tested vancomycin dilutions, with CD63 and CD203c expression exceeding negative and positive controls. These findings confirm vancomycin hypersensitivity and underscore the BAT's utility as a reliable in vitro diagnostic tool, especially in settings where skin testing or specific IgE assays are unavailable. This case highlights the BAT's potential for broader adoption in clinical allergy practice, particularly in resource-limited environments. It emphasizes the importance of reliable diagnostic methods for managing drug hypersensitivity in high-risk patients.