The detection of clonal rearrangements of the immunoglobulin heavy chain gene by the polymerase chain reaction provides a rapid method to differentiate monoclonal from polyclonal B-lymphocyte proliferations. It has been shown to be highly specific and so far, no false-positive results have been described. A case of a poorly differentiated colonic adenocarcinoma that showed a "false positive" clonal immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction technique is reported. DNA contamination was unlikely because of the strict adherence to the laboratory polymerase chain reaction protocol and also the repeated demonstration of the same amplified band in a separate experiment using DNA extracted from another piece of tumor tissue. The apparent monoclonal immunoglobulin heavy chain gene rearrangement in the first polymerase chain reaction may be related to a combination of the paucity of lymphoid cells in the tissue sample and the presence within this small number of lymphocytes of a clonal reactive cell population. It is, therefore, important to correlate the routine microscopic and immunohistochemical findings in the interpretation of polymerase chain reaction results, especially when working with nonlymphoid tumors and lymphocyte-poor lesions.