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Inflammatory breast cancer (IBC), an aggressive and lethal breast cancer subtype, lacks unequivocal genomic differences or robust biomarkers that differentiate it from non-IBC. Here, TGIRT-seq revealed myriad differences in tumors, PBMC, and plasma RNAs that distinguished IBC patients from non-IBC patients and healthy donors across different tested breast cancer subtypes. By mapping reads to genome and transcriptome reference sequences and quantitating intron-to-exon read depth ratios (IDRs), we developed methods for parallel analysis of transcriptional and posttranscriptional gene regulation. This analysis identified numerous protein-coding genes in IBC patient tumors and PBMCs with high IDRs, suggesting rate-limiting RNA splicing that decreases mRNA production. Mirroring gene expression differences in tumors and PBMCs, overrepresented protein-coding gene RNAs in IBC patient plasma were largely intron RNA fragments, while those in non-IBC patient and healthy donor plasma were largely mRNA fragments. Our findings provide insights into IBC and should enable monitoring disease progression by liquid biopsy.