We examined signaling molecules of peripheral blood T lymphocytes obtained from women with breast cancer. In 6 of 14 patients, T lymphocytes displayed an impaired ability to translocate NFêB p65 (Rel‐A) following activation by anti‐CD3 and IL‐2. This observation was made despite normal cytoplasmic levels of the Rel‐A protein. We also detected abnormally low levels of the signaling molecules T‐cell receptor (TCR)‐ζ, ZAP‐70 and p56^lck in 4 of 14 breast cancer patients, i.e., defects in T‐cell signaling molecules. T lymphocytes from 6 of the 14 patients also exhibited an increased expression of the dual specificity phosphatase, map kinase phosphatase‐1 (MKP‐1). MKP‐1 inactivates MAP kinase and therefore may interfere with the activation of c‐jun and c‐fos. Abnormalities of 1 or more signaling molecules were found in 9 of 14 patients; however, only 3 patients had T cells that exhibited all 5 defects. Our data have implications for the detection of potentially dysfunctional T cells in patients with cancer. For example, the analysis of only 1 signaling molecule may allow patients with significant defects in T‐cell signaling to go unnoticed. Finally, despite impaired Rel‐A translocation, T cells were capable of transcribing IL‐2. Impairments in the translocation of Rel‐B and c‐Rel further suggest that the NFκB family members Rel‐A, Rel‐B and c‐Rel are not required for the transcription of IL‐2 in the peripheral T lymphocytes of patients with breast cancer. Int. J. Cancer 78:16–20, 1998.© 1998 Wiley‐Liss, Inc.