We hypothesize that the products of cellular oncogenes and antioncogenes are biomarkers of events related to cancer risk. This study uses monoclonal antibody technology to examine serum proteins which are immunologically related to ras oncogene and epidermal growth factor receptor proteins. We measured the prevalence of ras- and epidermal growth factor receptor-related proteins in stored and freshly frozen serum from cancer patients, male heavy smokers, and older healthy subjects. Work emphasized the attainment of inter- and intraobserver agreement between independent readings of immunoblot gels. Although we achieved acceptable levels of agreement, we uncovered evidence for blood collection and storage artifacts. Accounting for these artifacts, we compared 80 cancer patients and 188 middle-aged and older community controls and found a strong relationship (odds ratio = 11.1; 95% confidence interval, 6.0-20.6) between cancer and a M(r) 21,000 serum protein related to the ras oncogene product. These results indicate the need and importance of comprehensive pretesting of putative cancer biomarkers before use in applied or etiological epidemiological research.