Protein kinase C is a serine-threonine kinase that is exists as a family of 12 isoforms. Numerous studies have linked the PKC isoforms to the maintenance of a malignant phenotype, however the direct substrates and downstream targets of PKC are largely unknown. Specifically, the alpha isoform is reported to be involved in the motility signaling pathways of MDA MB- 231 cells, a metastatic human breast cancer cell line. This study was designed to investigate the expression levels of PKC alpha, PKC substrates and the PKC substrate MARCKS in human breast cancer cell lines. The cell lines were reported to be of varying metastatic potential. Immunoblot analysis and immunohistochemistry revealed differences in expression levels of PKC alpha, PKC substrates and MARCKS. In MDA 468 cells, the expression level of PKC alpha is low, however the expression level of MARCKS was high. These results indicate the role of the PKC isoforms in malignant phenotypes may be cell line specific. Further studies will be directed toward establishing PKC isoform profiles in each cell line and identification of substrates. The results from these studies could be useful when designing cancer drug therapies.