Administration of genetically modified T lymphocytes to cancer patients has increased exponentially over the past 15 years, and these cells have been given to many hundreds of patients. These studies have often used retroviral vectors, and, in sharp contrast to clinical trials using hematopoietic stem cells as targets, gene-modified T cells have not subsequently undergone malignant transformation. This has led to the impression that the more differentiated state of T lymphocytes may offer protection from retroviral mutagenesis. In this issue of Molecular Therapy, however, Heinrich and colleagues document the occurrence of T-cell lymphoma in RAG−/− mice transplanted with OT-1 transgenic T cells genetically modified with a gammaretroviral vector encoding the green fluorescent protein, suggesting that, although T cells may be relatively insensitive to malignant transformation by gammaretroviruses, they are not immune.1