Two cases of follicular lymphoma (FL) with numerous large cells resembling the lacunar and Hodgkin and Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma were studied to determine clonal relationships between the HRS-like cells and centrocytic and centroblastic (CCCB) cells. In both cases, CCCB cells were typical of FL; CD45RB, CD20, CD10 and BCL-2 positive. In case 1, the HRS-like cells were positive for CD45RB, CD20, CD10, CD30, OCT2, and BOB.1 and negative for CD15 and bcl-2. In case 2, the HRS-like cells were positive for CD30, fascin, CD20, OCT2, and BOB.1 and negative for CD45RB, CD10, CD15, and bcl-2. CCCB and single HRS-like cells were isolated by laser capture microdissection followed by polymerase chain reaction amplification and sequencing of immunoglobulin heavy chain gene rearrangements. In both cases, identical sequences were obtained from CCCB and HRS-like cells. These findings confirm that although the HRS cells and CCCB cells in these cases demonstrate morphologic and immunophenotypic divergence, they share a common cell of origin. These cases further highlight the potential diagnostic pitfall presented by FL with HRS-like cells.