An important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported a recombinant vaccinia‐based vaccine (Sig/E7/LAMP‐1) that demonstrated significant anti‐tumor effect in a subcutaneous tumor challenge model. In this study, we investigated the potency of the Sig/E7/LAMP‐1 vaccine in preventing and treating metastatic tumors. A tumor metastasis model was generated by injecting human papillomavirus type 16 (HPV‐16) E6/E7 expressing tumor cells, designated TC‐1, into the tail vein of syngeneic C57BL/6 mice. All the naive mice injected with 1 × 10⁶ TC‐1 cells developed tumors confined exclusively to the lungs within 1 month. For in vivo tumor prevention experiments, mice were vaccinated with Sig/E7/LAMP‐1 followed by tumor challenge. While tumor growth was observed in all of the mice (10/10) in the control groups, 8 of 10 vaccinated mice (80%) remained tumor‐free 2 months post‐tumor challenge. For in vivo treatment experiments, mice were first inoculated with TC‐1 cells and then vaccinated with Sig/E7/LAMP‐1. Treatment with Sig/E7/LAMP‐1 was effective in eliminating preexisting tumor cells in 4 of 5 vaccinated mice. Most importantly, treatment with Sig/E7/LAMP‐1 resulted in regression of fully established lung tumors in 50% (5/10) of vaccinated mice. Our data suggest that the Sig/E7/LAMP‐1 vaccine is effective in controlling the hematogenous spread of TC‐1 tumor cells. In addition, the TC‐1 lung metastasis model can be used to test the efficacy of various E6/E7‐specific vaccines and immunotherapeutic strategies. Int. J. Cancer 78:41–45, 1998.© 1998 Wiley‐Liss, Inc.