The aim of the present study was to assess the putative relationship between HERVs and colon cancer through a comparative analysis of HERV-H, -K (HML-2), and -P env and HERV-K (HML-2) pol transcription; HERV-K Pol and Env protein expression; and HERV-H, -K (HML-2), and -PLTR methylation levels in malignant tissues and negative surgical margins collected from patients with advanced-stage disease. Here, ERVW-1 is linked to malignant colon neoplasm.