Background An increased prevalence of benign lesions has been associated with the increased use of radiological tools in orthopedic practice. Purpose To investigate the inter-observer reliability of the radiographic detection of lesions on the proximal humerus between different observers. Material and Methods X-ray radiological examinations of 17,243 patients were performed by an orthopedic surgeon to assess the presence of proximal humeral bone lesions. After this initial screening, 201 patients with lesions were identified and these 201 scans were assessed by three different physicians: an orthopedic oncologist, an orthopedic surgeon, and a musculoskeletal radiologist. Of the 201 patients with lesions, 80 had magnetic resonance imaging in addition to X-rays and were assessed. The diagnosis of the lesions was determined by each participant according to their radiological appearance to assess inter-observer reliability. Results The prevalence of proximal humeral lesions was determined by the orthopedic surgeon to be 1.165% (201 of 17,243 patients). In 201 patients with a lesion, the mean age was 48 ± 17 years (range = 18–91 years). According to the assessments of the orthopedic oncologist, orthopedic surgeon, and musculoskeletal radiologist, the most common bone lesion identified was enostosis, with prevalence percentages of 53.7%, 59.7%, and 64.7%, respectively. A noteworthy consensus exists in the collective diagnosis of bone lesions among the three investigators, demonstrated by a substantial agreement with Fleiss’ κ at 0.74 ( P < 0.001). Conclusion There was remarkable agreement between the three investigators on the collective diagnosis of bone lesions. Enostosis was the most common bone lesion at the proximal humerus in our series.