The number of patients undergoing hematopoietic cell transplantation (HCT) for malignant or non-malignant disorders has increased steadily over the past four decades. An important and potentially devastating complication of HCT is the occurrence of subsequent malignant neoplasms (SMNs). This chapter discusses the three types of SMNs seen among patients undergoing HCT. The emphasis is on clinical presentation of these malignancies, the magnitude of risk and risk factors associated with their development, insights into their pathogeneses, and the treatment options and outcome of patients with these malignancies. The chapter concludes with a brief summary regarding surveillance recommendations for early detection of SMNs. Genetic instability is hypothesized to be an early event in the development of malignancy, allowing the accumulation of multiple mutations in the same cell over time, and evolution of a clonal malignant population.