Thiarabine was evaluated for antitumor activity in seven human leukemia, lymphoma, and myeloma xenograft models to explore the activity in hematological malignancies. Thiarabine was active against all of the human leukemia and lymphoma lines tested, being curative against HL-60 leukemia and AS283 lymphoma and effecting tumor regressions in CCRF-CEM, MOLT-4, and K-562 leukemia and RL lymphoma models, but did not exhibit any appreciable activity against RPMI-8226 myeloma. For the leukemia/lymphoma models, thiarabine was more efficacious than ara-C/palmO-ara-C (four models), clofarabine (three models), fludarabine monophosphate (five models), cladribine (four models), and gemcitabine (six models). Thiarabine warrants future clinical trials with leukemias/lymphomas. © 2012 Copyright Taylor and Francis Group, LLC.