Objectives. We aimed to characterise mosaic populations of pancreatic islet cells from patients with atypical CHI (CHI-A) and the expression profile of NKX2.2, a key transcription factor expressed in β-cells but suppressed in δ-cells in the mature pancreas. Patients/Methods. Tissue was isolated from three patients with CHI-A following subtotal pancreatectomy. CHI-A was diagnosed on the basis of islet mosaicism and the absence of histopathological hallmarks of focal- and diffuse CHI (CHI-D). Immunohistochemistry was used to identify and to quantify the proportions of insulin-secreting β-cells and somatostatin-secreting δ-cells in atypical islets and the results compared to CHI-D (n=3) and age-matched control tissue (n=3). Results. In CHI-A tissue, islets had a heterogeneous profile. In resting / quiescent islets - identified by a condensed cytoplasm and nuclear crowding, β-cells were reduced to <50% of the total cell numbers in n=65/70 islets, whereas δ-cell numbers were increased with 85% of islets (n=49/57) containing >20% δ-cells. In comparison, all islets in control tissue (n=72) and 99% of CHI-D islets (n=72) were composed of >50% β-cells and >20% δ-cells were only found in 12% of CHI-D (n=8/66), and 5% of control islets (n=3/60). Active islets in CHI-A tissue contained similar proportions of β-cells and δ-cells as control and CHI-D islets. Finally, when compared to active islets, quiescent islets had a 2-fold higher prevalence of SOM+/NKX2.2+ co-expressed cells. Conclusions. Marked increases in NKX2.2 expression combined with increased numbers of δ-cells, strongly imply that an immature δ-cell profile contributes to the pathobiology of atypical CHI.