Temozolomide is utilized as a treatment for a variety of solid tumors and has been associated with the development of selective lymphopenia. We evaluated the incidence of lymphopenia and opportunistic infections during treatment and up to 12 months following treatment discontinuation in a cohort of 39 patients receiving temozolomide for advanced neuroendocrine tumors. The incidence of Grade 3-4 lymphopenia was 46 percent after 4 months of therapy and remained at 30 percent or greater for 12 months following treatment discontinuation. The overall incidence of opportunistic infections was 10 percent, while among patients receiving therapy for > or =7 months, the incidence was 20 percent. Prophylaxis for Pneumocystis jiroveci pneumonia and varicella-zoster, as well as cytomegalovirus monitoring, should be considered in patients receiving temozolomide-based treatment.