Introduction: We report the development of acute lymphoblastic leukemia in a patient in whom temozolomide was used for the treatment of a brain tumor. Unlike that of other alkylating agents, the leukemogenic potential of temozolomide is considered to be very low, and very rarely are such cases reported. Case Presentation: A 26-year-old Pakistani man who was treated for glioblastoma with temozolomide in an adjuvant setting was diagnosed to have acute lymphoblastic leukemia one year after stopping temozolomide. Conclusion: Temozolomide is a highly active agent, used in the management of high-grade brain neoplasms. The agent is generally regarded to be safe, with an acceptable safety profile. Very few cases of myelodysplasia associated with temozolomide use have been reported. We report here the first case of acute lymphoblastic leukemia, which developed in a young man about one year after he finished taking temozolomide. This should provide further insight into a possible toxicity profile of this alkylating agent. This finding should be of interest to physicians in general and to medical oncologists in particular.