Mantle cell lymphoma and primary nodal marginal zone lymphoma are uncommon tumors thought to arise within discrete anatomic compartments of the B-cell follicle. We report an unusual composite lymphoma comprised of these two neoplasms within an isolated lymph node in a 72-year-old woman. Strikingly, both tumors were completely confined to the respective microanatomic sites of their proposed nonneoplastic lymphoid counterparts, in keeping with early detection of these lesions. The tumors were distinguished by a combination of morphologic, phenotypic, and cytogenetic findings, and the presence of dual, unrelated neoplasms was confirmed by molecular diagnostic studies. After local radiation treatment, there was no recurrence or evidence of systemic disease over more than 2 years. These findings underscore the unique characteristics of these B-cell tumors and support the notion that early in disease development both neoplasms are confined to the distinct anatomic compartments of their postulated normal B-cell counterparts.