Diagnosing acute pyelonephritis relies on the combination of historical, physical, and laboratory findings. Costovertebral angle tenderness is important, although its accuracy is unknown. Point-of-care ultrasound-guided palpation (sonopalpation) may aid clinicians in localizing pain to discrete anatomic structures in cases of suspected acute pyelonephritis lacking classic features. We describe three low-to-moderate pre-test probability cases wherein maximal tenderness was elicited by renal sonopalpation, aiding in the diagnosis of acute pyelonephritis. In a fourth case, absence of renal tenderness to sonopalpation in a patient exhibiting typical acute pyelonephritis features led to an alternate diagnosis. Therefore, renal sonopalpation may be useful in confirming or refuting suspected cases.