Background: Expensive treatments and a growing number of cancer patients have resulted in increased spending on cancer care. Within a framework we developed for measuring the value of quality improvement (QI), we describe the cost-effectiveness of improving compliance with cancer screening measures compared to other quality measures. Methods: We used our framework to examine 18 Healthcare Effectiveness Data and Information Set (HEDIS) 2010 quality measures, synthesize related cost-effectiveness (CE) data and describe measure-specific QI-adjusted incremental cost-effectiveness ratios (ICERs). For each measure we: 1) quantified current compliance; 2) reviewed literature for ICERs; 3) estimated per-person steady state cost and quality-adjusted life years (QALYs); 4) estimated affected population size; 5) estimated the cost of QI; and 6) calculated QI-adjusted ICERs at full compliance, defined as 95%. We assumed per-person QI costs did not change with compliance and varied this in sensitivity analyses. We compared QI-adjusted ICERs for 3 cancer screening measures to the remaining measures. Results: Published ICERs for the cancer screening measures were $43,180/QALY (breast), $5,102/QALY (cervix) and $15,173/QALY (colon) and for other measures from $195/QALY (drug treatment) to $35,616/QALY (flu shots). Incorporating QI costs for cancer screening measures gave QI-adjusted ICERs of $64,549/QALY (breast), $15,463/QALY (cervix) and $22,991/QALY (colon), respectively. Incorporating QI costs for all 18 measures resulted in QI-adjusted ICERs from $195/QALY (drug treatment) to $9,075,868/QALY(antidepressant management), with a median of $15,463/QALY. Reaching 95% compliance with the 3 cancer measures would cost $5.1 billion and add 160,000 QALYs ($32,640/QALY) and with all 18 measures would cost $13.4 billion and add 5.8 million QALYs ($2,313/QALY). Conclusions: Improving compliance with cancer screening may be cost-effective at a threshold of $50k/QALY, although improving care on all HEDIS measures may be even more cost-effective. Accurate assessment of the cost of increasing cancer screening requires integration of both the cost-effectiveness of the screening tests and the cost of the QI programs needed to change practice.