Granules in blasts are most typical of acute myeloblastic leukemia. However, there have been scattered reports of patients with acute lymphoblastic leukemia (ALL) that have lymphoblasts with azurophilic cytoplasmic granules. These reports do not describe immunologic markers or cytogenetics. We report five additional cases with detailed cytologic, immunologic, and cytogenetic studies. At diagnosis one of these patients had central nervous system disease, while the others had no unusual features. Four of the five patients attained remission. The blasts of all five patients contained distinct cytoplasmic azurophilic granules. The granules were negative for peroxidase and chloroacetate esterase and positive for PAS, acid phosphatase, alpha-naphthyl acetate esterase incompletely fluoride inhibited, alpha-naphthyl butyrate esterase, and in one case, Sudan black B. In the one patient studied by electron microscopy, characteristic lymphoblasts contained membrane-bound electron lucent inclusions, which stained positively with non-specific esterase. Immunologic markers showed a common ALL phenotype. Different cytogenetic abnormalities were seen in all cases. It is important to recognize the characteristics of this morphologic subtype of ALL in order to avoid a misdiagnosis of acute nonlymphocytic leukemia.