Tissue biopsy is the principal method used to diagnose tumors in a variety of organ systems. It is essential to maximize tumor yield in biopsy specimens for both clinical diagnostic and research purposes. This is particularly important in tumors where additional tissue is needed for molecular analysis to identify patients who would benefit from mutation-specific targeted therapy, such as in lung carcinomas. Inadvertent sampling of fibrotic stroma within tumor nodules contaminates biopsies, decreases tumor yield, and can impede diagnosis. The ability to assess tumor composition and guide biopsy site selection in real time is likely to improve diagnostic yield. Polarization sensitive OCT (PS-OCT) measures birefringence in organized tissues, such as collagen, and could be used to distinguish tumor from fibrosis. In this study, PS-OCT was obtained in 65 lung nodule samples from surgical resection specimens containing varying ratios of tumor and fibrosis. PS-OCT was obtained with either a custom-built helical scanning catheter (0.8 or 1.6mm in diameter) or a dual-axis bench top scanner. Strong birefringence was observed in nodules containing dense fibrosis, with no birefringence in adjacent regions of tumor. Tumors admixed with early, loosely-organized collagen demonstrated mild-to-moderate birefringence, and tumors with little collagen content showed little to no birefringent signal. PS-OCT provides significant insights into tumor nodule composition, and has potential to differentiate tumor from stromal fibrosis during biopsy site selection to increase diagnostic tumor yield.