Purpose <p>Adenoid cystic carcinoma (ACC) is a rare cancer that arises from the salivary glands. Recent studies have shown that prostate-specific membrane antigen (PSMA) expression is high in ACC. We conducted a prospective study to evaluate clinical factors associated with high [⁶⁸Ga]Ga-PSMA-11 uptake and to report preliminary therapeutic outcomes of ¹⁷⁷Lu-PSMA therapy in recurred or metastatic ACC.</p> Materials and methods <p>Thirty patients were prospectively enrolled. Any focal accumulation of [⁶⁸Ga]Ga-PSMA-11 not explained by physiological uptake was defined as pathological lesions. Clinicopathological features relevant for high [⁶⁸Ga]Ga-PSMA-11 uptake in recurred or metastatic ACC were analyzed. Therapeutic outcomes of patients who received ¹⁷⁷Lu-PSMA therapy under compassionate use were also reviewed as a secondary component.</p> Results <p>A total of 238 lesions were evaluated, and the SUV_max ranged between 0.9 and 11.0, showing mild to moderate PSMA uptake. Higher SUV_max was observed in lung and bone metastases. The longest tumor diameter (<i>R</i> = 0.190, <i>P</i> = 0.009) and tumor % growth rate (<i>R</i> = 0.220, <i>P</i> = 0.006) were significantly correlated with SUV_max. A longer duration from diagnosis was a relevant factor for high [⁶⁸Ga]Ga-PSMA-11 uptake. Seven patients received ¹⁷⁷Lu-PSMA therapy, but therapeutic outcomes were limited.</p> Conclusion <p>High [⁶⁸Ga]Ga-PSMA-11 uptake in recurred or metastatic ACC was associated with location of metastases, longer tumor diameter, high tumor % growth rate, and a longer duration from diagnosis. While ¹⁷⁷Lu-PSMA therapy was performed in a limited cohort and outcomes were preliminary, these findings provide exploratory insights into potential factors relevant for patient selection and warrant further investigation in larger studies.</p>