|| The silica cell walls of diatoms, which exhibit species-spe-cific micro- and nano- patterned structures are promising candidates for applications in nanotechnology. Previous studies revealed a number of silica cell wall-associated proteins involved in silica formation. However, molecular biological analyses toward understanding of diatom cell wall formation have been mostly limited to model diatom species and general silica formation process in diatoms is still incompletely understood. In this study, to gain a compre-hensive insight into diatom silica biomineralization, tran-scriptome data of three diatom species, Nitzschia palea, Achnanthes kuwaitensis and Pseudoleyanella lunata, were newly developed. The reads obtained from RNA sequencing were assembled into 31,946, 60,767 and 38,314 unique transcripts for N. palea, A. kuwaitensis and P. lunata, respectively. In order to identify the diatom-specific genes, three transcriptome data sets developed in this study and the protein-coding gene sets of five genome-sequenced diatoms were compared. The proteins shared only by eight diatom species that are predicted to possess an endoplasmic reticulum (ER)-targeting signal peptide were selected for further analyses. These include proteins showing homology to silicanin-1, a recently reported diatom-specific protein involved in silica formation, as well as a number of SET domain proteins. The SET domain proteins might be novel diatom-specific family of methyltransferases that may reg-ulate the function of silica formation related proteins or long chain polyamines. The genes encoding the diatom-specific SET domain proteins identified in this study, which were shown to respond to silicon were suggested to be implicated in silica biomineralization.