Various types of tumor suppressor genes (TSG) have been reported to be mutated in malignant lymphoma. Point mutation and deletion are the major mechanisms that inactivate TSG. Alterations of the p53 gene have been analyzed well in lymphoid malignancies, and point mutations have been proved to have an important role in the progression or aggressiveness of B cell lymphoma. Recently, the silencing of gene expression by DNA hypermethylation was proposed as an alternative mechanism in inactivation of TSG. The p73, p15INK4B, and p16INK4A genes are targets of such epigenetic alterations. The ATM, PTEN, and SNF5/INI1 genes are also reported to be mutated in T and/or B cell malignancies. Recurrent chromosomal deletion may indicate the loss of candidate TSGs in the deleted interval. Cytogenetic and molecular analyses have revealed frequent and recurrent hemizygous chromosomal deletions at 6p, 6q, and 13p in malignant lymphoma. These deleted intervals have been intensively investigated to identify the candidate TSG that imply the pathogenesis of malignant lymphoma. As mentioned above, many TSG are mutated in malignant lymphoma, and these alterations could be critical in the development and progression of lymphoma. Comprehensive study of TSG is essential to understand the biological characteristics of malignant lymphoma.