Vertebral osteomyelitis can be a diagnostic pitfall for physicians, since it is protean and often subtle in its clinical presentation. It can coexist with metastatic lesions or mimic vertebral bone metastasis. When it occurs in patients with breast cancer, who are prone to have bone metastasis, it can present perplexing diagnostic problems. Misdiagnosing vertebral osteomyelitis as bone metastasis or vice versa results in delayed diagnosis and inappropriate treatment and may cause serious morbidity. We emphasize this problem by presenting the cases of two patients with breast cancer whose clinical course was complicated by vertebral osteomyelitis. When the clinical course of breast cancer is different from this usual presentation, a different process should be suspected, and histologic diagnosis should be promptly sought. Fine-needle aspiration biopsy and culture of suspicious-appearing bony lesions is recommended as a rapid and reliable method of establishing a definite diagnosis in this circumstance.