BACKGROUND Increased susceptibility to bacterial infections is a hallmark of multiple myeloma (MM). Invasive infections with Streptococcus pneumoniae may be the first manifestation of underlying MM. Clinicians treating patients with invasive S. pneumoniae infections may consider searching for underlying MM in the presence of certain diagnostic findings. CASE REPORT A previously healthy 60-year-old man was referred from his general physician because of fever, cough, and chills despite treatment with clarithromycin. The patient had experienced night sweats, weight loss, and recurrent episodes of fever and cough during the last 3 months. Examination was significant for left-sided pulmonary rales. A chest X-ray showed a retrocardiac consolidation of the left lower lobe. The patient was started on empirical antimicrobial therapy for community-acquired pneumonia. Subsequently, blood and sputum cultures were positive for S. pneumoniae. Given the history of night sweats and weight loss, the discrepancy between elevated total protein and low albumin levels, and the diagnosis of pneumococcal bacteremia, multiple myeloma (MM) was suspected and confirmed by immunofixation and bone marrow biopsy. CONCLUSIONS This case showed that clinicians should be vigilant for features of MM, which are encountered during history (e.g., weight loss, bone pain) or routine laboratory workup (e.g., unexplained anemia, renal failure, hypercalcemia, or a discrepancy between elevated total protein and low albumin levels) in elderly patients presenting with invasive pneumococcal disease.