The present invention is a method distinguishing between head and neck squamous cell carcinoma and lung squamous cell carcinoma. In particular, a 10-gene classifier has been identified which can be used to distinguish between primary squamous cell carcinoma of the lung and metastatic head and neck squamous cell carcinoma. These genes include CXCL13, COL6A2, SFTPB, KRT14, TSPYL5, TMP3, KLK10, MMP1, GAS1, and MYH2. A panel of one or more of these genes, or proteins encoded thereby, can be used for early diagnosis and selection of an appropriate therapeutic treatment.