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The most fundamental region of the chromosome for maintaining accurate genome segregation and stability is the centromeric chromatin [1,2]. In this review, we will focus on centromere-derived RNAs (cenRNAs), a crucial component of centromere structure first identified over 40 years ago [3] but only recently investigated in detail. Indeed, centromeric transcription is necessary for the proper formation of CENP-A-containing centromeric chromatin (cen-chromatin) [[4], [5], [6], [7]] and for the formation of pericentromeric heterochromatin [8,9], and the transcripts play a role in the structure and function of the centromere–kinetochore interface [3,7,10]. Furthermore, cenRNA overexpression has been observed in some cancer patients [[11], [12], [13]] and has been shown to drive the formation of breast cancer in a mouse model system [14]. Together, these observations call for a more detailed appraisal of the composition …