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Hi, on the 2015 Fusion model, is there any reason why I can’t remove the small 128GB blade SSD and replace the 2TB mechanical HDD with a 2TB 2.5” SSD?

Totally doable. You could even leave the blade drive in there and still upgrade the HDD to a 2.5” SSD if you wanted. And then not have to muck around with getting the board out, just to take that drive out. Once the HDD is removed the Mac will recognize the SSD as a separate disk, rather than part of the fusion and you can just format it for extra storage. Or keep it as a boot drive and use the 2TB SSD for storage.

I think it should work but if you are removing the blade, why not upgrade it instead? It has faster speed.

Sure you can remove your current HDD and replace it with a 2.5” SATA drive iMac Intel 27" Retina 5K Display Hard Drive Replacement but the performance will be limited to the SATA I/O unlike the PCIe/NVMe interface. While having a large 2TB drive is nice you may find going with a smaller PCIe/NVMe drive and using it as your boot drive with your apps will give you better performance and use your current HDD as the data drive iMac Intel 27" Retina 5K Display Blade SSD Replacement