BACKGROUND Cancer presents a substantial hardship for patients and their families in multiple domains beyond health and survival. Relatively little is known about the economic impact of cancer. The authors present estimates of the aggregate effects of a cancer diagnosis on employment and income in a prospective, nationally representative sample of US adults. METHODS The authors used data from the 1990 through 2009 waves of the Panel Study of Income Dynamics, a nationally representative, prospective, population-based observational study with high-quality individual and family-level economic information. Age-adjusted, sex-stratified, individual fixed-effects regression models were used to derive estimates of the impact of cancer on employment, hours worked, individual income, and total family income. RESULTS Significant effects of cancer on all 4 outcomes were observed. The probability of a cancer patient being employed dropped by almost 10 percentage points, and hours worked declined by up to 200 hours in the first year after diagnosis. Annual labor-market earnings dropped almost 40% within 2 years after diagnosis and remained low, whereas total family income declined by 20%, although it recovered within 4 years after the diagnosis. These economic impacts on survivors were driven by effects among men; the effects among women largely were not statistically significant. CONCLUSIONS A cancer diagnosis has substantial effects on the economic well-being of affected adults and their families. With the increasing number of cancer survivors in the US population, there is a growing need for examining the long-term implications for economic well-being and ways to mitigate the economic hardship associated with cancer. Cancer 2015;121:4425?32. © 2015 American Cancer Society.