The detection of several intracranial tumors among employees in one building complex (C500) at a petrochemical research facility prompted investigation of a possible workplace cause. This retrospective follow-up study included 1847 subjects, of whom 1735 had worked in C500. Medical records, death certificates, and Illinois State Cancer Registry data confirmed self-reported cancers and tumors. Analyses compared the subjects' cancer and benign intracranial tumor incidence rates with national general population rates. C500 employees had 15% fewer than expected total cancers (92 observed/108 expected; standardized incidence ratio [SIR], 85; 95% confidence interval [95% CI], 69 to 104). An excess of brain cancer (6/2.0; SIR, 302; 95% CI, 111 to 657) was concentrated among white men who had 10 or more years since hire and 5 or more years of C500 employment (4/0.7; SIR, 602; 95% CI, 165 to 1552) and who had worked in a particular building of C500 (5/0.7; SIR, 735; 95% CI, 239 to 1716). An excess of benign intracranial tumors (6/1.6; SIR, 385; 95% CI, 142 to 839) was not restricted to a single type of tumor and was not concentrated in any particular building. Occupational exposure may have caused the increased rate of brain cancer but is a less likely explanation for the elevated rate of benign intracranial tumors.