We examined the toxicity/efficacy of capecitabine with thalidomide, administered over 21-day cycles, in 24 previously treated metastatic breast cancer (MBC) patients. This regimen was poorly tolerated: grade 3/4 neutropenia (13%); grade 3 nausea (22%), vomiting (17%), and diarrhea (13%); and grade 2/3 hand-foot syndrome (38%). In addition, the response rate was lower than expected: partial response (13%), stable disease (17%), and progressive disease at first evaluation (35%). The median time to progression and overall survival were 2.7 and 11.0 months, respectively. These results do not support further investigation of thalidomide for MBC. The role of angiogenesis inhibition in breast cancer treatment should continue to be defined using more efficacious and specific inhibitors.