Kaposi's sarcoma-associated herpesvirus (KSHV), also referred to as human herpesvirus-8 (HHV-8), is a tumor causing virus. KSHV is the cause of several disease conditions known as Kaposi's sarcoma, multicentric Castleman disease, and primary effusion lymphoma. Cell culture supernatants from KSHV infected hematopoietic cells induced angiogenic tubule formation to a significantly greater extent than uninfected hematopoietic cells. Raman spectrum profiles were generated to differentiate the uninfected from KSHV infected cells. In general, profiles from all the hematopoietic cells shared similar peaks; however, the relative abundance of specific components varied significantly between the cells. Subsequent use of the multivariate analysis of the Raman spectra revealed significant differences between the uninfected and the KSHV infected cells. Taken together, this study reports the use of Raman tweezers to distinguish and analyze the biological relevance of KSHV infected cell signaling.