Purpose <p>This systematic review aimed to synthesize the available clinicopathological data on nasopalatine duct cyst (NPDC).</p> Methods <p>Electronic searches were performed in seven databases and the grey literature, according to the PRISMA 2020 statement. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. Data were analysed using descriptive statistics.</p> Results <p>A total of 168 studies comprising 2,734 NPDC cases were included. Most lesions were asymptomatic (<i>n</i> = 358/54.16%) and occurred in males (<i>n</i> = 1641/60.75%), with individuals in the fourth and fifth decade of life being the most frequently affected. Periapical radiographs (<i>n</i> = 181/40.31%) and computed tomography scan (<i>n</i> = 159/35.41%) were the most commonly used imaging modalities. Metaplasia (<i>n</i> = 278/58.28%) was observed in most cases with a predominance of combinations involving stratified squamous epithelium and pseudostratified ciliated columnar epithelium (<i>n</i> = 78/47.27%). The periapical cyst was the second most frequent clinical diagnostic hypothesis. Enucleation was the preferred treatment modality (<i>n</i> = 544/95.94%), and recurrence was absent in most cases (<i>n</i> = 375/93.05%).</p> Conclusion <p>NPDC is a benign lesion with a heterogeneous clinical presentation and a low recurrence rate. Its anatomical location frequently results in diagnostic overlap with odontogenic lesions, particularly periapical chronic lesions. Clinicians should be aware of its clinicopathological features and integrate clinical, radiographic, and histopathological findings to ensure accurate diagnosis and appropriate management.</p>