The ATRA syndrome, now commonly referred to as differentiation syndrome (DS), is a distinct clinical entity. This patient had many features of DS: unexplained fever, dyspnea, weight gain of > 5 kg, peripheral edema, pleural effusions, and interstitial infiltrates. Other features may include unexplained episodic hypotension and peripheral edema, pericardial effusion, and renal failure. The signs and symptoms of this syndrome are commonly encountered in hospitalized patients with hematologic malignancy; therefore, other causes must be ruled out before the diagnosis of DS can be made. This includes an assessment for congestive heart failure and cardiac disease, sepsis, diffuse alveolar hemorrhage, other pneumonias or infections, and other causes of renal failure. The radiographic abnormalities of DS are listed in Table 1.