Purpose: Although seizures are relatively common in acute childhood leukemias, evolution into epilepsy is rare. Methods: We describe three patients with acute leukemias who received chemotherapy. One patient also received cranial irradiation. Results: All three developed recurrent complex partial seizures after initiation of chemotherapy. Initial neuroimaging performed in two patients was normal. Subsequent neuroimaging in all three revealed mesial temporal sclerosis. Conclusions: The association of mesial temporal sclerosis in acute childhood leukemias has not been previously described and may be secondary to antileukemic treatment and recurrent seizures.