Recent studies suggest US medical schools are not effectively addressing musculoskeletal medicine in their curricula. We examined if there were specific areas of weakness by analyzing students' knowledge of and confidence in examining specific anatomic regions. A cross-sectional survey study of third- and fourth-year students at Harvard Medical School was conducted during the 2005 to 2006 academic year. One hundred sixty-two third-year students (88% response) and 87 fourth-year students (57% response) completed the Freedman and Bernstein cognitive mastery examination in musculoskeletal medicine and a survey eliciting their clinical confidence in examining the shoulder, elbow, hand, back, hip, knee, and foot on a one to five Likert scale. We specifically analyzed examination questions dealing with the upper extremity, lower extremity, back, and others, which included more systemic conditions such as arthritis, metabolic bone diseases, and cancer. Students failed to meet the established passing benchmark of 70% in all subgroups except for the others category. Confidence scores in performing a physical examination and in generating a differential diagnosis indicated students felt below adequate confidence (3.0 of 5) in five of the seven anatomic regions. Our study provides evidence that region-specific musculoskeletal medicine is a potential learning gap that may need to be addressed in the undergraduate musculoskeletal curriculum.