STUDY DESIGN: Resident's case problem. BACKGROUND: Although rare in the general population, bone and soft tissue tumors may be more frequently encountered in patients seeking physical therapy because of the propensity of their initial symptoms to mimic those of commonly treated musculoskeletal disorders. Screening for tumors requires the physical therapist to be attentive to unexpected findings. The purpose of this paper was to describe the clinical-reasoning and screening processes of physical therapists who facilitated the timely recognition of bone and soft tissue tumors in 3 patients referred through medical channels. DIAGNOSIS: The referral diagnoses were lumbar spinal stenosis, calcaneal bursitis, and postexcisional quadriceps weakness. When comprehensively examined, each of the patients had either atypical examination findings or failed to respond to physical therapy treatment. After the physical therapists alerted the appropriate medical providers of the examination findings, diagnoses of high-grade osteosarcoma of the pelvis, chondroma of the knee, and liposarcoma of the thigh followed. DISCUSSION: Tumors of the lower extremity can initially mimic common musculoskeletal pathology. Physical therapists must remain alert for red flags, atypical signs and symptoms, and poor responses to treatment, even when patients are referred through medical channels. Particular attention is necessary in the case of unusual symptoms in the lower extremity, where over half of primary malignant tumors occur.