Hormone-sensitive lipase (LIPE) plays a fundamental role in the regulation of energy balance by releasing free fatty acids from adipose triacylglycerol stores. These fatty acids can be subsequently transferred to other body compartments to be oxidized or employed in other biochemical reactions. This enzymic function is particularly important in lactating animals because the synthesis of milk components involves the mobilization of lipid depots to satisfy the large energy demands of the mammary gland. In the current study, we partially sequenced the goat LIPE gene in several individuals. In doing so, we identified two synonymous polymorphisms at exons 2 (c.327C>A>T, triallelic polymorphism) and 3 (c.558C>T). Moreover, we found a mis-sense polymorphism at exon 6 (c.1162G>T) that involves an alanine to serine substitution at position 388. Analysis with Polyphen and Panther softwares revealed that this amino acid replacement is expected to be neutral. Performance of an association analysis with a variety of milk traits revealed that goat LIPE genotype has highly suggestive effects on milk yield (P=0·0032) as well as on C18:3 n-6g (P=0·0051), trans-10 cis-12 CLA (P=0·007) and C12:0 (P=0·0084) milk contents. These associations are concordant with the preference of LIPE to selectively mobilize medium-chain and unsaturated fatty acids.