The oncoprotein, bcl-2, is expressed in various types of non-Hodgkin's lymphoma (NHL). Immunodetection of this protein is a useful method for distinguishing follicular hyperplasia from follicular lymphoma. Although bcl-2 might also be a useful marker for distinguishing reactive monocytoid B-cell hyperplasia from its putative malignant counterpart, marginal zone lymphoma, there were no extensive studies to date that tested this. Therefore, we performed a survey of bcl-2 expression in 778 cases of NHL using immunohistochemical techniques applied to routinely processed and paraffin-embedded tissues. Of 20 reactive monocytoid B-cell hyperplasias, none were bcl-2 positive, compared with 118 (79%) of 150 marginal zone lymphomas (P = .001). With respect to the follicular lymphomas in our study, of the 110 Grade I lymphomas, 107 (97%) were bcl-2 positive, 119 (83%) of the 143 Grade II lymphomas were positive, and 71 (74%) of the 96 Grade III lymphomas were positive. The bcl-2 positivity of Burkitt-like high-grade B-cell lymphoma was significantly different from that of Burkitt's lymphoma (4 [67%] of 6 vs. 0 of 5; P = .02). T-cell NHL had a significantly lower bcl-2 positivity than did B-cell NHL (10 [45%] of 22 vs. 627 [83%] of 756; P = .0001). Therefore, bcl-2 is a highly sensitive marker for follicular lymphoma and a useful marker for distinguishing reactive monocytoid B-cell hyperplasia from marginal zone lymphoma The significant difference in bcl-2 positivity between Burkitt-like high-grade B-cell lymphoma and Burkitt's lymphoma suggests an additional diagnostic use for this protein.