Background: The 18-gene expression profile, ColoPrint, has been developed and validated for identifying risk of recurrence in patients with early stage colon cancer (CC). In a pooled stage 2 validation study ColoPrint identified 63% of patients as Low Risk with a 3-yr recurrence free survival (RFS) of 93% while High Risk patients had a 3-yr RFS of 82% with a HR of 2.7 (p=0.001). PARSC is a prospective study for the assessment of recurrence risk in stage II CC patients using ColoPrint. ColoPrint classification is compared to NCCN risk classification. Methods: The study enrolled 501 patients with histologically proven stage 2 CC from 31 institutes in Europe, USA, and Asia between October 2008 and September 2013. Synchronous tumors were excluded. ColoPrint results were not disclosed to the physician and patient. Treatment was at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative. A McNemars test is performed to compare ColoPrint with NCCN risk classification. A p- value ≤ 0.05 indicates the two tests differ significantly. Results: ColoPrint classified 352 (70%) patients as Low Risk and 149 (30%) as High Risk. 97 patients (19%) received adjuvant chemotherapy. In the ColoPrint Low Risk group, 66 (19%) patients received adjuvant chemotherapy and 31 (21%) of ColoPrint High Risk patients received chemotherapy. According to NCCN high risk factors (T4, high grade (exclusive of MSI-H), lymphovascular/perineural invasion, perforation/obstruction, <12 nodes examined, positive margins) 274 (55%) patients were NCCN Low Risk and 227 were NCCN High Risk. 82 (30%) of the NCCN Low Risk patients are ColoPrint High Risk. 160 (70%) of the NCCN High Risk patients are ColoPrint Low Risk. MSI-status was assessed in 96 (18%) patients of which 33 were MSI high and 63 were MSS. All MSI high were classified as ColoPrint Low Risk. Conclusions: The PARSC study is the first prospective study to compare genomic and clinical risk assessment and we observed marked differences between NCCN risk classification and ColoPrint. The clinical validity of these methods will be based on the outcomes at 3 and 5 years. Clinical trial information: NCT00903565.