Background: The cost of cancer treatment has increased significantly in recent decades, but it is unclear whether these costs have been associated with commensurate improvement in clinical value. This study aimed to assess the association between the cost of cancer treatment and 4 of the 5 NCCN Evidence Blocks (EB) measures of clinical value: efficacy of regimen/agent, safety of regimen/agent, quality of evidence, and consistency of evidence. Methods: This is a cross-sectional, observational study. We obtained NCCN EB ratings for all recommended, first-line, and/or maintenance treatments for the 30 most prevalent cancers in the United States and calculated direct pharmacologic treatment costs (drug acquisition, administration fees, guideline-concordant supportive care medications) using Medicare reimbursement rates in January 2019. We used generalized estimating equations to estimate the association between NCCN EB measures and treatment cost with clustering at the level of the treatment indication. Results: A total of 1,386 treatments were included. Among time-unlimited treatments (those administered on an ongoing basis without a predetermined stopping point), monthly cost was positively associated with efficacy ($3,036; 95% CI, $1,782 to $4,289) and quality of evidence ($1,509; 95% CI, $171 to $2,847) but negatively associated with safety (–$1,470; 95% CI, –$2,790 to –$151) and consistency of evidence (–$2,003; 95% CI, –$3,420 to –$586). Among time-limited treatments (those administered for a predetermined interval or number of cycles), no NCCN EB measure was significantly associated with treatment cost. Conclusions: An association between NCCN EB measures and treatment cost was inconsistent, and the magnitude of the association was small compared with the degree of cost variation among treatments with the same EB scores. The clinical value of cancer treatments does not seem to be a primary determinant of treatment cost.