High dose chemotherapy with autologous stem cell transplantation (ASCT) is increasingly used in the treatment of patients with lymphoma. As previously shown with conventional treatments, second neoplasms are emerging as a long term complication of the procedure. In this study, we investigate the incidence of second neoplasm in a cohort of 171 patients treated with BEAM or BEAC regimens for Hodgkin's disease (n = 62) and non-Hodgkin's lymphomas (n = 109) followed up for a median of 52 months post ASCT. Six patients developed six second malignancies 12 to 105 months after ASCT: fibrolamellar carcinoma of the liver, malignant fibrous histiocytoma, pancreatic carcinoma, squamous cell carcinoma of the lung, invasive carcinoma of the vulva and acute myelogenous leukemia. The cumulative actuarial risk for developing second malignancy is 16.7% (95% confidence interval: 5.9-39.3%) 13 years after transplant. The age-adjusted incidence of cancer in the study group is 4.1 times higher than that of primary cancer in the general population. These data confirm that ASCT recipients are at increased risk of later malignancies. This complication adds significant morbidity and mortality to the transplant process and therefore, needs to be taken into account in long term evaluation of new strategies which involve early intensification in the treatment of lymphomas.