Haematological toxicity characterized by delayed and reversible neutropenia and/or thrombocytopenia is an adverse effect observed in 40% of patients receiving fotemustine. We report the case of a 66-year-old man with metastatic malignant melanoma treated with fotemustine as monotherapy. A severe persistent and prolonged thrombocytopenia occurred, so that chemotherapy was discontinued. Bone marrow involvement was excluded. The physician should be aware of this prolonged thrombocytopenia secondary to fotemustine, so that it may be recognized early and not attributed erroneously to tumour evolution. This observation could be substantial for the design of combination regimens with fotemustine and other myelotoxic drugs in pretreated melanoma patients.