Unexplained unintentional weight loss (UUWL) is a common health problem in older adults, and raises significant diagnostic challenges. Currently, there is no consensus or guideline to help physicians approach these patients. The main purpose of this study is to evaluate physicians’ behaviors in evaluating elderly patients with UUWL and to compare the diagnostic strategy of internists and geriatricians. From January of 2008 to December of 2009, medical records of all elderly patients admitted to Taipei Veterans General Hospital with UUWL were obtained for study. All diagnostic procedures used during admissions were evaluated and the final diagnosis for each patient was obtained. Overall, data of 136 patients (mean age: 79.8 ± 6.3 years, 80.9% males) were obtained for study with their mean weight loss of 8.6 ± 6.4 kg. Among them, 79 (58.1%) patients were admitted to the geriatric evaluation and management unit (GEMU) and 57 (41.9%) patients were admitted to the general medical wards. There were no statistically significant differences in terms of age, sex, mean age and average weight loss between these two groups. After extensive diagnostic effort, the most common diagnostic entity was benign organic disease (33.8%), followed by unknown (25.7%), neuropsychiatric disorder (23.5%), and malignancy (16.9%). Tumor markers are commonly used, including carcinoembryonic antigen (CEA) (80.9%), prostate specific antigen (PSA) (81.8%), and carbohydrate 19-9 (CA 19-9) (65.4%). Imaging studies were also commonly used diagnostic tools, including gastrointestinal endoscopy (70.6%), colonoscopy (42.6%) and computerized tomography (44.1%). Compared with internists, geriatricians were more likely to order PSA testing (70.5% vs. 89.4%, p = 0.021). In contrast, internists were more likely to order CA-199 (75.4%% vs. 58.2%, p = 0.045), and to arrange gastrointestinal endoscopy than geriatricians (82.4% vs. 62.0%%, p = 0.013). In conclusion, cancer accounts for only 16.9% of all elderly patients with UUWL in this study, tumor markers are very commonly used for screening of occult cancer. Compared with internists, geriatricians are more likely to order PSA and to establish neuropsychiatric diagnosis, and internists are more prone to order carbohydrate (CA 19-9) and gastrointestinal endoscopy.