Hi Remi - since you say you have clinical tissue samples I assume the tissue blocks are PFA-fixed and stored in either fixative, or buffer or 70% ethanol. The issue is not to waste tissue, right, meaning that you want to be able to use them for other purposes? Would it be possible to dissect them, or rather divide them with a section plane corresponding to what you want to analyze histologically? Then you have one intact tissue piece left; the other piece - whether paraffin-embedded or cryoprotected and frozen – can be stored for further sectioning after you have sampled the sections you need.
Then, making 4-5 µm sections… If paraffin embedding is compatible with what you want to do, it is excellent for sections of that thickness. Cryo-sectioning is possible at that thickness in a cryostat, but decidedly more difficult and so with a greater risk for tissue “waste”.
As for positioning: with both paraffin embedding and embedding in cryomounting medium for freezing, just orient your piece of tissue so you can mount it on the microtome specimen holder with the plane of interest facing the knife.
I hope this may be some help – best of luck!