Rabbit monoclonal antibodies (RabMAbs) represent a novel category of immunoreagents that may combine the best properties of both mouse monoclonal antibodies (MMAs) and rabbit antisera. In the attempt to verify the performance of this new class of antibodies on paraffin-embedded tissue, RabMAbs against estrogen receptor, progesterone receptor, Ki-67, cyclin D1, CD3, CD5, CD23, and synaptophysin were tested on several tumor types as well as normal tissues. The results were compared with those obtained with classic MMAs against the same antigens. RabMAbs appear to offer increased sensitivity with no apparent loss of specificity. On routine use they permit higher working dilutions (5 to 10 times on average), allowing significant improvement in terms of laboratory efficiency. The robustness of RabMAbs is further proved by the fact that in some instances optimal staining can be obtained even without antigen retrieval. In consideration of the high performance observed, routine use of RabMAbs may contribute significantly to standardize diagnostic immunohistochemical procedures.