| Basis of differentiation | Polyclonal antibodies | Monoclonal antibodies |
| Definition | Refer to a combination of immunoglobulin molecules derived by different clones of plasma B cells | Refer to identical immunoglobulins that are derived from a single clone of plasma B cells |
| Produced by | Different clones of plasma B cells | The same clone of plasma B cells |
| Cost to produce | Inexpensive | More expensive |
| Population of antibodies | Heterogeneous population of antibodies | Homogenous population of antibodies |
| Production requirement | Hybridoma cell lines are not required | Hybridoma cell lines are required |
| Origin | Multiple lineages of stimulated B cells | Single lineage of stimulated B cells |
| Cross reactivity | Higher cross-reactivity due to biophysical diversity | Lower cross-reactivity due to higher specificity |
| Binding specificity | Recognizes and binds to multiple epitopes on the same antigen | Recognizes and binds to a single epitope on the target antigen |
| Applications | Widely used in general research applications | Used mainly for therapeutic purposes |
| Advantages | Higher antibody affinity, multiple epitope binding, higher tolerance to minor changes in epitope structure, and more robust detection | Batch-to-batch consistency, single-epitope binding, high specificity, high reproducibility |
| Disadvantages | No single-epitope binding, batch-to-batch variation, higher likelihood of cross-reactivity, higher false positives because of higher sensitivity | Potential to exhibit cell drift over time, low tolerance to minor changes in antigen epitope structure, limited applications because of mono-specificity |