Objectives <p>To investigate the diagnostic performance of quantitative parameters derived from Dual-layer spectral detector CT (DLCT) in distinguishing between mucinous adenocarcinoma (MC) and adenocarcinoma not otherwise specified (AC) in colorectal adenocarcinoma (CRAC).</p> Materials and methods <p>Patients with pathologically confirmed CRAC who underwent preoperative DLCT scanning were enrolled in this retrospective study from May 2022 to September 2024. A propensity score-matching (PSM) approach was employed to balance the important patient characteristics between the MC group and the AC group. DLCT quantitative parameters were compared between the MC and AC groups, and a multifactorial binary logistic stepwise forward regression analysis was conducted to identify independent factors. Receiver operating characteristic (ROC) curves were utilized to evaluate diagnostic efficacy.</p> Results <p>A total of 260 patients were enrolled in this study. Following PSM, 23 patients with MC and 23 patients with AC were included in the analysis. All DLCT parameters were significantly lower in patients with MC compared to those with AC (all <i>p</i> &lt; 0.01). Electron density (OR = 0.007, 95% CI: 0.000–0.295) and normalized iodine concentration (OR = 0.000, 95% CI: 0.000–0.067) in the venous phase were identified as independent predictors associated with different histopathological types. The combination of these two spectral parameters demonstrated significantly superior diagnostic efficacy compared to conventional CT attenuation values (<i>p</i> &lt; 0.05), achieving an area under the curve of 0.949, with a sensitivity of 87.0% and a specificity of 91.3%.</p> Conclusions <p>Quantitative spectral parameters derived from DLCT can effectively differentiate MC from AC preoperatively, exhibiting excellent diagnostic efficacy.</p> Critical relevance statement <p>DLCT is a reliable diagnostic tool to preoperatively differentiate pathological types of colorectal cancer, thereby facilitating personalized treatment strategies.</p> Key Points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>This study investigated the value of dual-layer spectral CT (DLCT) in differentiating the pathological types of colorectal cancer.</p> </ItemContent> <ItemContent> <p>Quantitative spectral parameters demonstrated excellent accuracy in the diagnosis of mucinous adenocarcinoma.</p> </ItemContent> <ItemContent> <p>Preoperative DLCT can help clinicians in formulating personalized treatment strategies.</p> </ItemContent> </UnorderedList></p> Graphical Abstract <p></p>