S100 calcium-binding protein A6 (S100A6) is a protein that in humans is encoded by the S100A6 gene.  The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in stimulation of Ca2+-dependent insulin release, stimulation of prolactin secretion, and exocytosis. Chromosomal rearrangements and altered expression of this gene have been implicated in melanoma.

S100A6 is a cytoplasmic and nuclear protein abundantly expressed in fibroblasts and epithelial cells. It is also detected in some neurons, glial cells, smooth muscle, myocytes, and lymphocytes. S100A6 has been studied in many human tumors, including pancreatic, melanocytic, gastric, and colorectal cancers. In pancreatic cancer, elevation of S100A6 RNA and protein has been observed in malignant cells. Nuclear S100A6 expression is associated with reduced survival time in pancreatic cancer patients. S100A6 expression is also significantly correlated with melanoma metastases and survival times. It has been shown to be upregulated in 50% of gastric cancers, and highly expressed at the invasive margins of colorectal carcinoma. S100A6 has also been reported as possible diagnostic marker of papillary thyroid carcinoma.