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We describe a successful desensitization to alemtuzumab in one patient diagnosed with T-cell prolymphocytic leukaemia. Alemtuzumab treatment was initiated during infusion number 18, the patient showed cutaneous eruption with a miliary pattern, despite premedication with corticosteroids and antihistamines. The eruption returned with successive alemtuzumab infusions (infusions 19, 20 and 21), remained present for longer and was more severe with each infusion. The patient was referred to our Allergy Unit as it was necessary to maintain alemtuzumab treatment. Total immunoglobulin E level was 3 UI/ml and specific immunoglobulin E against more common pneumo-allergens, food, latex and hamster were inferior to 0.35 UI/ml. Prick test using the undiluted drug (30 mg/ml) and intradermal tests using serial dilutions (1/10, 1/100) were performed. The result of alemtuzumab skin prick test was 4 mm. The intradermal skin test result was positive at 1/100 dilution (papule: 8 mm; erythema: 12 mm). The basophil activation test with alemtuzumab was performed concluding that 10% of the basophils were activated by alemtuzumab. The patient underwent alemtuzumab desensitization according to a 12-step protocol that resolved to be safe and efficacious. Our experience may be helpful for similar clinical cases where the therapeutic options are very limited and a life-threatening condition such T-cell prolymphocytic leukaemia is present. In addition, a careful risk/benefit ratio should be considered and accurate informed consent is mandatory.