Purpose: Prostate cancer incidence and mortality levels in African-American men are the highest among all ethnic groups. This points to the role of biological factors in driving disparate outcomes. Here, we are investigating the molecular signature differences leading to prostate cancer differences in African American (AA) vs. Caucasian American (Cau) patients, using Raman spectroscopy. Methods: After IRB approval, tissue samples from two demographic groups (AA and Cau patients) were collected. Each group consists of n = 10 cancer patients and n = 4 healthy control samples (total number of samples, n = 28). We acquired 20 Raman spectra per patient (Total = 560 spectra), using a Renishaw inVia Reflex Raman spectrometer, with an excitation wavelength (λex) of 532nm, a laser power of 5% (1.5mW), and an exposure time of 10 seconds per spectrum. Raman spectra were analyzed using Multivariate curve resolution alternating least square (MCRALS) analysis, to quantify the biomolecular differences in the normal and cancer samples between the two groups. Results: The results showed an increase in the total protein level in AA patients compared to Cau patients. We observed an increase in unsaturated lipid and total protein and a decrease in collagen in AA patients compared to Cau patients. Furthermore, higher protein and lower collagen in AA means more aggressive PCa. The unsaturated lipid (component 1) and protein scores of AA cancer patients are higher than those found in Cau cancer patients. However, the saturated lipid score (component 2) and collagen level in AA cancer patients are found to be lower than that of Cau cancer. Conclusion: The spectral profiles obtained through MCR-ALS analysis of Raman spectra of prostate tissue samples revealed major peaks corresponding to lipid, protein, and collagen. The results of this biomolecular imaging of clinical samples may advance racial disparity research in prostate cancer.