Invasive properties of tumor cells having acquired heavy metal resistance were investigated. We selected the cadmium-resistant (Cd-R) cells from human fibrosarcoma HT-1080 cells. Total metallothionein levels in cytosol of HT-1080 Cd-R cells were significantly higher than original lines, and were of a highly resistant potency to cytotoxicity of cisplatin, as well as heavy metals. The HT-1080 Cd-R cells showed higher invasiveness into recombinant basement membrane Matrigel. However, HT-1080 Cd-R cells were inferior in locomotion ability. Significant differences in adhesive ability to extracellular matrix proteins were not observed between HT-1080 and HT-1080 Cd-R cells. High invasiveness of HT-1080 Cd-R cells was caused by their extremely strong enzymatic activities. High level of 92kDa matrix metalloproteinase-9 (MMP-9) was recognized from the conditioned medium of HT-1080 Cd-R cells, whereas 72kDa MMP-2 was secreted equally from both cell lines. Our investigation suggests that drug resistance acquired through the mechanisms of cellular metal-tolerance may promote malignancy and tumor metastasis during cancer chemotherapy.