Transcriptomes from stem-inoculated Scots pine saplings were analyzed to identify unique and enriched H. annosum transcripts in the early stages of infection. Comparing different time points since inoculation identified 131 differentially expressed H. annosum genes with p-values of ≤0.01. Our research supports the results of previous studies on the Norway spruce–Heterobasidion annosum s.l. pathosystem, indicating the role of carbohydrate and lignin degradation genes in pathogenesis at different time points post-inoculation and the role of lipid metabolism genes (including but not limited to the delta-12 fatty acid desaturase gene previously reported to be an important factor). The results of this study indicate that the malic enzyme could be a potential gene of interest in the context of H. annosum virulence. During this study, difficulties related to incomplete reference material of the host plant species and a low proportion of H. annosum transcripts in the RNA pool were encountered. In addition, H. annosum transcripts are currently not well annotated. Improvements in sequencing technologies (including sequencing depth) or bioinformatics focusing on small subpopulations of RNA would be welcome.