Purpose <p>Non-contrast MRI characteristics can help differentiate mucin plugs from mural nodules in pancreatic cystic lesions. To identify MRI features that differentiate non-enhancing lesions from true mural nodules in pancreatic cystic lesions.</p> Materials and methods <p>We retrospectively evaluated 90 patients with pancreatic cystic lesions containing 101 nodular components (62 non-enhancing, 22 benign enhancing, 17 high-risk). Two experienced radiologists independently assessed multiple non-contrast MRI characteristics, including signal-intensity patterns, shape, and their cyst-wall relationship. The reference standard was the contrast-enhanced pattern, with histopathology for resected specimens or minimum 2-year stability for presumed mucin plugs. Diagnostic performance was evaluated in binary logistic regression models.</p> Results <p>Only the non-enhancing lesions (41.9%) showed the “target sign” (layered appearance due to different central- and peripheral-portion signal intensities), providing 100% specificity for identifying non-enhancing lesions. The non-enhancing lesions were predominantly oval-shaped (93.5%) with posterior-wall attachment (85.5%), whereas enhancing lesions showed a complex morphology. On diffusion-weighted imaging (DWI), 93.5% of the non-enhancing lesions showed low signal intensity and 95.2% showed high apparent diffusion coefficient<b> (</b>ADC) values, contrasting with high DWI signal (82.4%) and low ADC values (82.4%) in the high-risk lesions. A multiparameter model achieved excellent diagnostic performance with an area under the curve of 0.97 for differentiating non-enhancing from enhancing lesions and 0.92 for distinguishing non- or benign enhancing from high-risk lesions.</p> Conclusions <p>Non-contrast MRI features, particularly the target sign, shape characteristics, and cyst-wall relationship can reliably differentiate mucin plugs from true mural nodules in pancreatic cystic lesions, potentially reducing unnecessary invasive procedures.</p>