Tamoxifen (TAM) and toremifene (TOR) are two antiestrogen agents frequently used in the treatment of breast cancer. They are currently being assessed as the prophylactic for patients at high risk of developing tumors. However, the side effects of these drugs on memory function have drawn attention in clinical usage. In the present study, it is demonstrated in mice that TAM and TOR significantly shortened the escaping latency or increased the number of errors, respectively, by using the step-down and step-through passive avoidance tests. By using an appetitively motivated task in T-maze, it is demonstrated that TAM and TOR significantly delayed the latency of finding food in well-trained mice. TAM appeared to impair memory consolidation and retrieval processes, rather than acquisition of memory, whereas TOR appeared to impair acquisition, consolidation, and retrieval processes. These results provide experimental support for the clinical findings that have shown that these drugs impaired memory function in patients routinely taking the drugs and suggest that caution should be taken for using these drugs as the prophylactics for those at risk of developing tumors.