Buccal cell usage has been shown by many to be a cost effective and safe method to isolate DNA for various biological experiments especially large epidemiological studies (Garcia-Closas et al. Cancer Epidemiol Biomarkers Prev 10:687-696, 2001). Non-invasive DNA collection methods are preferred over phlebotomy in order to increase study participation and compliance in research centers and for sick patients in hospital settings. There have been conflicting reports about the methodology and results obtained from using buccal DNA. It is not very clear if phlebotomy can be confidently replaced by buccal cell DNA. It is often left for the user to take an intelligent decision. To address this issue, we compared the performance of buccal and blood DNA from same subjects in a genotyping experiment and this paper reports the results. Cotton swab derived buccal cells were scraped from the inner side of cheeks from 16 subjects, and blood was also drawn from the same 16 subjects participating in a genotypic association study of a lipid disease. The DNA quality was assessed by resolving on agarose gels, checking purity (A260/A280) and finally by microarray hybridization. This study showed that DNA degradation affects the total yield and performance of the buccal DNA when compared to the blood DNA in microarray based genotyping. Genotyping results can be seriously compromised if care is not taken to check the quality and yields of such specimens.