In recent years, Karyopherin α 2 (KPNA2) has emerged as a potential biomarker in multiple cancer forms. The aberrant high levels observed in cancer tissue have been associated with adverse patient characteristics, prompting the idea that KPNA2 plays a role in carcinogenesis. This notion is supported by studies in cancer cells, where KPNA2 deregulation has been demonstrated to affect malignant transformation. By virtue of its role in nucleocytoplasmic transport, KPNA2 is implicated in the translocation of several cancer-associated proteins. We provide an overview of the clinical studies that have established the biomarker potential of KPNA2 and describe its functional role with an emphasis on established associations with cancer.