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Anomalous course and tenosynovitis of extensor pollicis longus (EPL) tendon is a rare condition that presents clinical symptoms very similar to de Quervain's disease. Herein we report a case of anomalous course and tenosynovitis of the extensor pollicis longus (EPL) tendon associated with symptoms of de Quervain's disease.A 44-year-old right-handed man visited the clinic because of radial pain associated with the left wrist, which was aggravated during the previous 10 days. The patient tested positive on the Finkelstein's test and displayed a limited range of motion of the left wrist. Motion of the thumb and wrist aggravated pain.Magnetic resonance imaging (MRI) of the left wrist suggested mild tenosynovitis at the third extensor compartment and intersection syndrome. However, clinical symptoms failed to match the MRI findings.A zig-zag skin incision on the radial styloid process was made. The operative findings revealed stenosing tenosynovitis with partial tearing. Retraction of the tendon extended the thumb interphalangeal joint, suggesting that the tendon was the EPL tendon rather than EPB tendon. After operation, we reviewed the MRI of the patient, which revealed that the oblique course of the EPL tendon originated from the ulnar side of the forearm to the radial styloid at the radial and proximal site of Lister's tubercle. No EPB tendon was present.At 12 months of follow-up, the patient's radial styloid process was completely asymptomatic and resumed full daily activities.Anomalous course of the EPL tendon is rarely reported associated with similar symptoms of de Quervain's disease. However, the knowledge and understanding of this potential anomaly in the course of EPL tendon is very important for the treatment of de Quervain's disease to decrease patient dissatisfaction after surgery.