diff --git a/src/libslic3r/Print.cpp b/src/libslic3r/Print.cpp
index e8078931b..ebd2e8f66 100644
--- a/src/libslic3r/Print.cpp
+++ b/src/libslic3r/Print.cpp
@@ -22,6 +22,7 @@
 #include <boost/filesystem/path.hpp>
 #include <boost/format.hpp>
 #include <boost/log/trivial.hpp>
+#include <boost/regex.hpp>
 
 // Mark string for localization and translate.
 #define L(s) Slic3r::I18N::translate(s)
@@ -438,7 +439,8 @@ static inline bool sequential_print_vertical_clearance_valid(const Print &print)
     return it == print_instances_ordered.end() || (*it)->print_object->height() <= scale_(print.config().extruder_clearance_height.value);
 }
 
-
+// Matches "G92 E0" with various forms of writing the zero and with an optional comment.
+boost::regex regex_g92e0 { "^[ \\t]*[gG]92[ \\t]*[eE](0(\\.0*)?|\\.0+)[ \\t]*(;.*)?$" };
 
 // Precondition: Print::validate() requires the Print::apply() to be called its invocation.
 std::string Print::validate(std::string* warning) const
@@ -652,6 +654,18 @@ std::string Print::validate(std::string* warning) const
 		            	return err_msg;
         }
     }
+    {
+        bool before_layer_gcode_resets_extruder = boost::regex_search(m_config.before_layer_gcode.value, regex_g92e0);
+        bool layer_gcode_resets_extruder        = boost::regex_search(m_config.layer_gcode.value, regex_g92e0);
+        if (m_config.use_relative_e_distances) {
+            // See GH issues #6336 #5073
+            if (! before_layer_gcode_resets_extruder && ! layer_gcode_resets_extruder)
+                return "Relative extruder addressing requires resetting the extruder position at each layer to prevent loss of floating point accuracy. Add \"G92 E0\" to layer_gcode.";
+        } else if (before_layer_gcode_resets_extruder)
+            return "\"G92 E0\" was found in before_layer_gcode, which is incompatible with absolute extruder addressing.";
+        else if (layer_gcode_resets_extruder)
+                return "\"G92 E0\" was found in layer_gcode, which is incompatible with absolute extruder addressing.";
+    }
 
     return std::string();
 }