ABSTRACT: Milk fatty acids secreted by the mammary gland are one of the most important determinants of the nutritional value of goat milk. Unlike cow milk, limited data are available on the transcriptome-wide changes across stages of lactation in dairy goats. In this study, goat mammary gland tissue collected at peak lactation, cessation of milking, and involution were analyzed with digital gene expression (DGE) sequencing to generate longitudinal transcript profiles. A total of 51,299 unigenes were identified and further annotated to 12,763 genes, of which 9,131 were differentially expressed across various stages of lactation. Most abundant genes and differentially expressed genes (DEGs) were functionally classified through clusters of euKaryotic Orthologous Groups (KOG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A total of 16 possible expression patterns were uncovered, and 13 genes were deemed novel candidates for regulation of lactation in the goat: POLG, SPTA1, KLC, GIT2, COPS3, PDP, CD31, USP16/29/37, TLL1, NCAPH, ABI2, DNAJC4, and MAPK8IP3. In addition, PLA2, CPT1, PLD, GGA, SRPRB, and AP4S1 are proposed as novel and promising candidates regulating mammary fatty acid metabolism. "Butirosin and neomycin biosynthesis" and "Glyoxylate and dicarboxylate metabolism" were the most impacted pathways, and revealed novel metabolic alterations in lipid metabolism as lactation progressed. Overall, the present study provides new insights into the synthesis and metabolism of fatty acids and lipid species in the mammary gland along with more detailed information on molecular regulation of lactogenesis. The major findings will benefit efforts to further improve milk quality in dairy goats.