The role of S100A4 in tumor progression and metastasis is well documented in numerous research articles and summarized in several reviews [1-3]. Currently S100A4 is categorized as an essential metastasispromoting factor whose production and secretion from “activated” stromal cells (fibroblasts, immunocytes and vascular cells) is initiated and stimulated by signals derived in tumor cells (cytokines, growth factors and others). However recent data gained from experimental and clinical studies significantly extend our knowledge on S100A4. Implications of S100A4 in various non-malignant pathological conditions have been demonstrated by number of research groups. In the mini-review we attempted to highlight the role of S100A4 in other than cancer important human pathologies, such as autoimmune inflammation (RA) and disorders in cardio-vascular, nervous and pulmonary systems. We suggest that diverse human diseases might have common molecular components and pathway(s). Possibly, inflammatory machinery and S100A4 as its intrinsic constituent could contribute to the pathogenesis of various disorders. Therefore, we presume that facts on S100A4 performance could be attractive for broad range of researchers and clinicians.