The diagnostic potential of PCR-based studies on the immunoglobulin heavy chain (IgH) gene rearrangements and the t(14;18) translocation was evaluated in a series of 30 benign and 46 malignant follicular lymphoid lesions including difficult problem cases using formaldehyde-fixed and paraffin-embedded (FFPE) tissue. Clonal IgH gene rearrangement was documented by PCR in 38/46 follicular lymphomas using two alternative (FR3A and FR2A-based) primer systems: all benign hyperplasias showed a polyclonal pattern. The t(14;18) translocation was documented in 20/46 cases, including cases that did not show a clonal IgH gene amplification; a weak signal was seen in 6 benign hyperplasias probably related to the recently described rare non-neoplastic cells carrying the t(14;18) translocation. Of the translocations in follicular lymphomas, 18 involved the major breakpoint region (MBR) and two the minor cluster region (MCR). The diagnosis of follicular lymphoma could be reached with at least one marker in over 90% of the cases. With these tests we diagnosed an incidental follicular lymphoma in the axillary dissection for breast carcinoma, and confirmed benign nature of an extreme follicular hyperplasia with a 2200 g spleen. One diffuse large cleaved cell lymphoma with subsequent follicular small cleaved cell lymphoma was diagnosed to have a similar t(14;18) translocation showing a link between the two seemingly different lymphomas.