Introduction: It is recommended that genetic testing be offered to all patients with familial and apparently sporadic pheochromocytoma (PC) and/ or paraganglioma (PGL) as germline mutations may be detected in up to 30 % of cases. In addition to VHL, RET, NF1, SDHA, SDHB, SDHC, SDHD SDHAF2, MAX and FH testing, TMEM127 mutation analysis has been added to decision algorithms which assist in prioritizing genetic testing, a lengthy and costly process in PC/PGL patients. Typically most patients with TMEM127 mutations present with unilateral disease (bilateral in 28%), almost exclusively benign adrenal PC with an average age of 41.5 years and few cases with metastases. We report here four novel TMEM127 variants of likely pathogenic significance. Patients. Patient 1(P1) presented at age 39 years (having experienced relevant symptoms for many years) with no family history, raised catecholamines and underwent surgery for bilateral PCs; P2 had an adrenal PC removed at age 52 years; P3 with a family history of renal cell carcinoma, underwent surgery for adrenaline- and noradrenaline- secreting bilateral PC at age 54 years; and P4, a 57 year old was diagnosed with a composite PC and ganglioneuroma with a history of hyperparathyroidism. Methods. Genomic DNA from the four patients was sequenced by a combination of Sanger and/or targeted massively parallel sequencing. All potentially pathogenic variants were verified by Sanger sequencing (of two samples) and clinical significance of variants predicted by ‘in silico’ programs. None of the four patients harboured RET, VHL, SDHD or SDHB mutations. Results. Four novel TMEM127 variants were identified each with a different clinical presentation. The following variants were identified: exon 4 insertion; deletion of 3 nucleotides in exon 4; deletion of 4 nucleotides in exon 2; missense mutation in exon 2. Conclusion. This report expands the genetic and phenotypic spectrum of TMEM127 mutation-associated PC/PGL.