Should all women with node-negative breast cancer receive chemotherapy? Acceptance of such a broad recommendation has been controversial due to the relatively good prognosis of these women and the lack of evidence of an improvement from chemotherapy in overall survival. We studied the question with a decision analytic model, which simulates a clinical trial of a large number of women over several decades, to calculate quality-adjusted life expectancy and the cost-effectiveness of chemotherapy in 45-year-old and 60-year-old women. The model considered a variety of scenarios about the long-term benefits of chemotherapy. The initial analysis found a lifetime benefit of 4 to 5 quality months (range, 2 to 14 months) at a cost of $15,400 to $18,800 per quality year (range, $5,100 to $56,800). If a risk-stratification protocol could identify a low-risk group, then benefit drops to about 1 quality month at a cost of $65,000 to $90,000 per year. For the average woman, chemotherapy increases the quality-adjusted life expectancy by a substantial amount at a generally acceptable cost. However, given the uncertainty of the duration of benefit and current potential for risk-stratification, a broad recommendation for chemotherapy is inappropriate.