Autocrine growth factors for the epidermal growth factor receptor (EGFR) have been identified in prostate tumors, implicating a role for EGFR in the progression of prostate cancer. To investigate early signaling mechanisms used by the EGFR in prostate tumor cells, we have characterized the involvement of the Shc (src homology 2/x‐collagen related) adapter protein in EGFR signaling in several human prostate tumor cell lines. In androgen‐responsive lymph node‐prostate cancer (LNCaP) cells and androgen‐insensitive PC3, DU145 and PPC‐1 cells, Shc was identified as one of the most prominent phosphotyrosine proteins to be elevated in response to EGF. Equivalent levels of the 46‐ and 52‐kDa Shc isoforms were detected in all of the tumor cell lines tested. However, levels of the 66‐kDa isoform were variable among the cell lines. In all of the tumor cell lines, EGF caused an association between Shc and Grb2, another adapter protein linked to cellular ras activation. Additionally, several phosphotyrosine proteins, including a 115–120‐kDa protein in EGF‐treated LNCaP cells, co‐associated with Shc. The profile of these Shc‐associating proteins, however, differed among the tumor cell lines. Our results indicate that Shc is a common downstream element of EGFR signaling in prostate tumor cells and suggest multiple functions for Shc in prostate tumorigenesis. Int. J. Cancer 77:923–927, 1998.© 1998 Wiley‐Liss, Inc.