We evaluated the usefulness of a new scintigraphic sign, a quantum mottling pattern, in diagnosing right-to-left shunt using 99mTc-MAA particles. The quantum mottling pattern is characterized by random distribution of discrete clumps of radioactivity that are more intense than the general body background. Forty-nine 99mTc-MAA scintigrams were analyzed retrospectively for presence of a quantum mottling pattern in extrapulmonary soft tissues and brain. This distinctive pattern was observed in every patient (18/18) in whom a right-to-left shunt was confirmed by nonscintigraphic means and was noted only in one patient in whom independent proof of a right-to-left shunt was not available. In contrast, application of conventional criteria yielded a true-positive interpretation for 15/18 patients with right-to-left shunts and a false-positive interpretation for another four patients. Presence of a quantum mottling pattern on 99mTc-MAA images appears to be a reliable aid for detecting a right-to-left shunt. Use of this sign is likely to improve accuracy of the scintigraphic test in patients with small shunts.