Since variations regarding cell‐type distribution on the patient level were detected, the present results may suggest an immune response associated with patient‐specific parameters like implant biofilm/oral microbiome composition, different implant surface characteristics, different anatomical features like bone quality and soft tissue condition, different and/or combined etiology pathways and individual genetic and epigenetic immunological conditions. Further, the histological samples may have been taken at a different stages of peri‐implant inflammation, a classification between clinical diagnostic parameters and histological appearance seems difficult. In the field of periodontology it is well accepted that patient individual genetic and epigenetic patterns lead to a different immunological potential based on histone modification and DNA methylation with varying expression levels of cytokines, chemokines and toll‐like receptors of the oral epithelia. For peri‐implantitis similar mechanisms are suspected but not sufficiently examined. Orthopedic studies revealed typical histological patterns in low‐ and high‐grade infections around orthopedic prostheses consisting of neutrophil granulocytes, plasma cells as well as small lymphocyte aggregates, whereas in particle‐induced aseptic lesions macrophages and multinucleated giant cells can occupy more than 20% of the lesion depending on particle size and configuration. High amounts of macrophages (up to 26%) in some patients of the present study may suggest a particle/ion related etiology for this patient subgroup. Tissue retrieval studies in orthopedics found a predominance of M1 macrophages in response to wear particles and an in‐vitro study based on genome‐wide microarray and a multiplex cytokine assay demonstrated that the response to titanium particles is determined by the state of macrophage polarization. Recent studies demonstrated a specific immunological macrophage polarization pattern comparing periodontitis and peri‐implantitis lesions whereas peri‐implantitis lesions display a higher number of macrophages coupled with a distinct macrophage pro‐inflammatory M1 polarization signature. A particle‐triggered mechanism involved in peri‐implantitis lesions around titanium implants is being discussed, but an unidirectional causal relationship between titanium particles in the peri‐implantitis lesions and onset or progression of peri‐implantitis disease has not been proven. Influence of metal particles and ions on peri‐implant biofilm and their possible role in the development, formation and production of extracellular polysaccharides is discussed in current research. In the peri‐implant mucosa of zirconia ceramic implants, zirconia elements have been detected as well, however the origin and influence of metal or ceramic ions or particles on peri‐implantitis remains unclear.