This paper offers a comprehensive discussion of the cardinal numeral system of Italian Sign Language. At the lexical level, we present the different formational strategies used to generate cardinal numerals and we provide evidence that in the younger generations of signers, the sign one has lost the function of indefinite determiner and is now used as a cardinal only. At the syntactic level, we show that the attested variation in the ordering between the cardinal and the noun is in part due to definiteness and contrastive focus. We account for this variation within the cartographic approach to syntax. Finally, we offer a principled explanation for the reason why cardinals inside Measure Phrases are not subject to word order variation, but always precede the measure noun.