Phorbol ester tumor promoters activate protein kinase C (PKC) isozymes and novel non-kinase receptors, suggesting a high degree of complexity in the signaling mechanisms of tumorigenesis. Many studies have shown that PKC isozymes contribute to the progression of malignant phenotype. We review the emerging understanding of the roles of PKC isozymes in the three sequential cellular processes of tumor invasion and metastasis: attachment to extracellular matrix or basement membrane components, matrix degradation by proteolytic enzymes, and migration through the digested matrix. In addition, we discuss the potential role of chimaerins, novel non-kinase phorbol ester receptors, in carcinogenesis.