Recent studies suggest that PRL-3 is involved in the metastasis of colorectal cancer, but the mechanism concerning that has not been well defined. This article expresses PRL-1, PRL-2, and PRL-3 and the catalytically inactive mutant forms of those enzymes in SW620 and SW480 cells, two human cell lines derived from non-metastatic cancer and metastatic colorectal cancer, respectively. While the expression of the native forms of PRLs promotes the spreading, adhesion, and proliferation of these cells, the expression of their mutant forms inhibits the earlier-mentioned processes. These data thus provide a cellular mechanism for the role of PRL-3 in tumor metastasis and suggest that all the three PRLs have similar functions. Recent studies suggest that PRL-3 is involved in the metastasis of colorectal cancer, but the mechanism concerning that has not been well defined. This article expresses PRL-1, PRL-2, and PRL-3 and the catalytically inactive mutant forms of those enzymes in SW620 and SW480 cells, two human cell lines derived from non-metastatic cancer and metastatic colorectal cancer, respectively. While the expression of the native forms of the native forms of PRLs promotes the spreading, adhesion, and proliferation of these cells, the expression of their mutant forms inhibits the earlier-mentioned processes. These data thus provide a cellular mechanism for the role of PRL-3 in tumor metastasis and suggest that all the three PRLs have similar functions.