Protein tyrosine phosphatases (PTPs) are important in the regulation of diverse cellular functions including proliferation, migration and invasion; aberration of these cellular events is crucial for the development and progression of cancer. PTPs family comprises of two groups, classic PTPs and dual specificity phosphatases. The classic PTPs include both non-transmembrane PTPs and transmembrane receptor-like PTPs (RPTPs). RPTPs are composed of extracellular regions, transmembrane domains and intracellular phosphatase domains. The extracellular regions of RPTPs are similar to cell adhesion molecules and can interact homophilically and heterophilically. There are eight subgroups in the RPTPs separated according to the differences in their extracellular regions. PTPRK and PTPRM belong to the R2B subfamily of RPTPs and both perform homophilic interactions and regulate cell-cell aggregation and adhesion. Furthermore, both PTPRK and PTPRM can interact with the catenin/cadherin complex to regulate cell proliferation and migration. The current review discusses the present knowledge on RPTPs and their potential implication in the development and progression of cancer.