Women who receive uninformative BRCA1/2 genetic test results face ongoing uncertainty about their future cancer risks. This article prospectively examined the influence of intolerance for uncertainty and perceived breast cancer risk on psychological distress following the receipt of uninformative BRCA1/2 test results. Sixty-four women who received uninformative BRCA1/2 mutation test results completed measures of Intolerance for Uncertainty, perceived breast cancer risk, and measures of cancer-related, genetic testing, and general distress. Cancer-related (ΔR2 = 0.18, P ≤ 0.001), general (ΔR2 = 0.04, P ≤ 0.05), and genetic testing distress (ΔR2 = 0.12, P ≤ 0.01) were associated with intolerance for uncertainty at 1 month post-disclosure. The interaction of intolerance for uncertainty and breast cancer perceived risk predicted cancer-related (ΔR2 = 0.10, P ≤ 0.001) and genetic testing distress (ΔR2 = 0.09, P ≤ 0.01) at 6 months post-disclosure. Distress was highest among patients with highest perceived risk and intolerance for uncertainty, suggesting that those who have difficulty coping with their ambiguous risk are at risk for long-term distress. The clinical and research implications of these results are discussed. © 2006 Wiley-Liss, Inc.