Lead is classified as a possible carcinogen in humans. We studied the relationship of blood lead level and all cancer mortality in the general population of the United States using data from the National Health and Nutrition Examination Survey II (NHANES II) Mortality Study, 1992, consisting of a total of 203 cancer deaths (117 men and 86 women) among 3,592 whites (1,702 men and 1,890 women) with average of 13.3 years of follow-up. We used Cox proportional hazard regression models to estimate the dose-response relationship between blood lead and all cancer mortality. Log-transformed blood lead was either categorized into quartiles or treated as a continuous variable in a cubic regression spline. Relative risks (RRs) were estimated for site-specific cancers by categorizing lead above and below the median. Among men and women combined, dose-response relationship between quartile of blood lead and all cancer mortality was not significant (ptrend = 0.16), with RRs of 1.24 [95% percent confidence interval (CI), 0.66-2.33], 1.33 (95% CI, 0.57-3.09), and 1.50 (95% CI, 0.75-3.01) for the second, third, and fourth quartiles, respectively, compared with the first quartile. Spline analyses found no dose response (p = 0.29), and none of the site-specific cancer RRs were significant. Among men, no significant dose-response relationships were found for quartile or spline analyses (p trend = 0.57 and p = 0.38, respectively). Among women, no dose-response relationship was found for quartile analysis (ptrend = 0.22). However, the spline dose-response results were significant (p = 0.001), showing a threshold effect at the 94th percentile of blood lead or a lead concentration of 24 microg/dL, with an RR of 2.4 (95% CI, 1.1-5.2) compared with the risk at 12.5 percentile. Because the dose-response relationship found in women was not found in men, occurred at only the highest levels of lead, and has no clear biologic explanation, further replication of this relationship is needed before it can be considered believable. In conclusion, individuals with blood lead levels in the range of NHANES II do not appear to have increased risk of cancer mortality.