It is estimated that 10 to 20% of all genes in the human genome encode cell surface proteins and due to their subcellular localization these proteins represent excellent targets for cancer diagnosis and therapeutics. Therefore, a precise characterization of the surfaceome set in different types of tumor is needed. Using TCGA data from 15 different tumor types and a new method to identify cancer genes, the S-score, we identified several potential therapeutic targets within the surfaceome set. This allowed us to expand a previous analysis from us and provided a clear characterization of the human surfaceome in the tumor landscape. Moreover, we present evidence that a three-gene set-WNT5A, CNGA2, and IGSF9B-can be used as a signature associated with shorter survival in breast cancer patients. The data made available here will help the community to develop more efficient diagnostic and therapeutic tools for a variety of tumor types.