The Mucin 1 (MUC1) oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis, and extracellular matrix remodeling. A set of experimentally derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature predicts significant decreases in both disease-free and overall survival in patients with breast (n=295) and lung (n=442) cancers. The data show that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients.