Colorectalcancer(CRC)isthethirdmostcommoncancerinmenandthesecondmostcommoncancerinwomen,worldwide.Intheearlystagesofthedisease,biomarkerspredictingearlyrelapsewouldimprovesurvivalrates.Inmetastaticpatients,theuseofpredictivebiomarkerscouldpotentiallyresultinmorepersonalizedtreatmentsandbetteroutcomes.TheCXCfamilyofchemokines(CXCL1to17)aresmall(8to10kDa)secretedproteinsthatattractneutrophilsandlymphocytes.Thesechemokinessignalthroughchemokinereceptors(CXCR)1to8.Severalstudieshavereportedthatthesechemokinesandreceptorshavearoleineitherthepromotionorinhibitionofcancer,dependingontheircapacitytosuppressorstimulatetheactionoftheimmunesystem,respectively.Ingeneralterms,activationoftheCXCR1/CXCR2pathwayortheCXCR4/CXCR7pathwayisassociatedwithtumoraggressivenessandpoorprognosis;therefore,thespecificinhibitionofthesereceptorsisapossibletherapeuticstrategy.Ontheotherhand,thelesserknownCXCR3andCXCR5axesaregenerallyconsideredtobetumorsuppressorsignalingpathways,andtheirstimulationhasbeensuggestedasawaytofightcancer.Thesepathwayshavebeenstudiedintumortissues(usingimmunohistochemistryormeasuringmRNAlevels)orserum[usingenzyme-linkedimmunosorbentassay(ELISA)ormultiplexingtechniques],amongothersampletypes.CommonvariantsingenesencodingfortheCXCchemokineshavealsobeeninvestigatedaspossiblebiomarkersofthedisease.ThisreviewsummarizesthemostrecentfindingsontheroleofCXCchemokinesandtheirreceptorsinCRCanddiscussestheirpossiblevalueasprognosticorpredictivebiomarkersaswellasthepossibilityoftargetingthemasatherapeuticstrategy.