This study investigated the extent to which intolerance of uncertainty was associated with cancer worry interference, anxiety and depression among women with Lynch syndrome (LS), and whether having greater trust in one’s physician moderated those relationships. Women with confirmed LS (N = 128) were recruited from a high-risk of cancer registry and completed a one-time self-report questionnaire. Women who reported greater intolerance of uncertainty and more trust in their physician reported less cancer worry interference compared to women who had greater intolerance of uncertainty and less trust in their physician, who reported the highest worry interference, b = −1.39, t(99) = −2.27, p = .03. No moderation effect of trust in physician was found for anxiety or depression. Trust in one’s physician buffered the impact of high intolerance of uncertainty on cancer worry interference, underscoring the need for supportive provider–patient relationships, particularly for LS patients.