Taking into consideration the 105 potential liquid biopsy biomarkers that were identified in serum, we herein reported the best five serum biomarkers that display excellent diagnostic accuracy: CMIP, GAD1, NME1, CDS1, and CKS1B. Importantly, these novel potential biomarkers might constitute better CCA biomarkers than CA19-9 since the AUC values that we herein obtained (up to 0.891) are higher than the diagnostic capacity reported in a systematic review and a meta-analysis, in which the AUC value for CA19-9 was 0.830 [42]. The gene discussed is NME1; the disease is cholangiocarcinoma.