Adjuvant chemotherapy is administered to cancer patients after curative resection but is unnecessary when patients without micro-metastatic lesions undergo a perfectly curative surgical procedure. Patients who need adjuvant chemotherapy are those with micro-metastases outside the resection area that are not detectable by imaging, despite curative resection at primary sites. If biomarkers that reflect metastatic potential could be developed, personalized adjuvant chemotherapy could be provided in clinical settings. Actinin-4 (ACTN4, gene name ACTN4) is an actin-bundling protein identified in 1998 as a novel molecule involved in cancer invasion and metastasis. Overexpression of actinin-4 protein in cancer cells leads to an invasive phenotype, and patients with gene amplification of ACTN4 have a worse prognosis than patients with a normal copy number for cancers of the pancreas, lung, and salivary glands, among others. This review summarizes the biological roles of actinin-4 in cancer invasion and metastasis and examines the potential usefulness of actinin-4 as a biomarker for evaluation of metastatic ability.