DICER1 syndrome is a complex autosomal dominant tumor predisposition disorder characterized by a distinct chronological progression of benign and malignant lesions. By mapping the transition from early-childhood pulmonary and renal manifestations to the adolescent emergence of endocrine and reproductive neoplasms, this review provides a longitudinal framework for clinical vigilance. Central to this analysis is the molecular "two-hit" mechanism, specifically investigating how somatic hotspot mutations in the RNase IIIb domain disrupt the miR-140/FGF9 signaling axis and the let-7 feedback loop. The review identifies the neomorphic "Argonaute strand switch" as a primary driver of pathogenesis, resulting in a diagnostic 3p-strand bias that fuels sarcomatous transformation. Beyond the molecular substrate, we define the critical radiographic and clinical markers of malignancy, such as rapid volumetric growth, cystic solidification, and the detection of somatic hotspots via high-sensitivity droplet digital PCR. By integrating the 2024 international surveillance standards with emerging technologies, including Vision Transformer-based radiographic analysis and circulating tumor DNA monitoring, this review offers a proactive, evidence-based roadmap for identifying the predictors of malignancy and better management of the disease. Ultimately, this synthesis aims to equip clinicians and other healthcare profesionals with the predictive tools necessary to achieve definitive cures while minimizing the cumulative clinical and psychological burden on this genetically vulnerable population.