diff --git a/Marlin/src/HAL/DUE/HAL.h b/Marlin/src/HAL/DUE/HAL.h
index 97b94b5db234ee05b446a8ecdfa0b53487779e58..90b6fabc050e7848c07884dad0527e048112cc71 100644
--- a/Marlin/src/HAL/DUE/HAL.h
+++ b/Marlin/src/HAL/DUE/HAL.h
@@ -94,7 +94,6 @@
   #endif
 #endif
 
-
 #include "MarlinSerial.h"
 #include "MarlinSerialUSB.h"
 
diff --git a/Marlin/src/HAL/DUE/MarlinSerial.cpp b/Marlin/src/HAL/DUE/MarlinSerial.cpp
index d827def4225115dba7ab410863c9aad2ceb611f8..d114c75989c44a403aa7bb9331ee801168782c76 100644
--- a/Marlin/src/HAL/DUE/MarlinSerial.cpp
+++ b/Marlin/src/HAL/DUE/MarlinSerial.cpp
@@ -629,23 +629,13 @@ void MarlinSerial<Cfg>::printFloat(double number, uint8_t digits) {
 
 // If not using the USB port as serial port
 #if SERIAL_PORT >= 0
-
-  // Preinstantiate
-  template class MarlinSerial<MarlinSerialCfg<SERIAL_PORT>>;
-
-  // Instantiate
-  MarlinSerial<MarlinSerialCfg<SERIAL_PORT>> customizedSerial1;
-
+  template class MarlinSerial<MarlinSerialCfg<SERIAL_PORT>>;      // Define
+  MarlinSerial<MarlinSerialCfg<SERIAL_PORT>> customizedSerial1;   // Instantiate
 #endif
 
-#ifdef SERIAL_PORT_2
-
-  // Preinstantiate
-  template class MarlinSerial<MarlinSerialCfg<SERIAL_PORT_2>>;
-
-  // Instantiate
-  MarlinSerial<MarlinSerialCfg<SERIAL_PORT_2>> customizedSerial2;
-
+#if defined(SERIAL_PORT_2) && SERIAL_PORT_2 >= 0
+  template class MarlinSerial<MarlinSerialCfg<SERIAL_PORT_2>>;    // Define
+  MarlinSerial<MarlinSerialCfg<SERIAL_PORT_2>> customizedSerial2; // Instantiate
 #endif
 
 #endif // ARDUINO_ARCH_SAM
diff --git a/Marlin/src/HAL/DUE/MarlinSerial.h b/Marlin/src/HAL/DUE/MarlinSerial.h
index eb26a5644dd90e66cbf466368d095bf8f3b7f05d..fa6a2c7d157a10694d0b4d633294ea7dda19763c 100644
--- a/Marlin/src/HAL/DUE/MarlinSerial.h
+++ b/Marlin/src/HAL/DUE/MarlinSerial.h
@@ -172,13 +172,9 @@ struct MarlinSerialCfg {
 };
 
 #if SERIAL_PORT >= 0
-
   extern MarlinSerial<MarlinSerialCfg<SERIAL_PORT>> customizedSerial1;
+#endif
 
-#endif // SERIAL_PORT >= 0
-
-#ifdef SERIAL_PORT_2
-
+#if defined(SERIAL_PORT_2) && SERIAL_PORT_2 >= 0
   extern MarlinSerial<MarlinSerialCfg<SERIAL_PORT_2>> customizedSerial2;
-
 #endif
diff --git a/Marlin/src/HAL/DUE/MarlinSerialUSB.cpp b/Marlin/src/HAL/DUE/MarlinSerialUSB.cpp
index 41ffb52ba112e17fc66c1b3a2d0dba7ed713f7fd..7a020bbaf0b1a157bc0541bac7e5c8d58504c571 100644
--- a/Marlin/src/HAL/DUE/MarlinSerialUSB.cpp
+++ b/Marlin/src/HAL/DUE/MarlinSerialUSB.cpp
@@ -29,7 +29,7 @@
 
 #include "../../inc/MarlinConfig.h"
 
-#if SERIAL_PORT == -1
+#if HAS_USB_SERIAL
 
 #include "MarlinSerialUSB.h"
 
@@ -283,8 +283,12 @@ void MarlinSerialUSB::printFloat(double number, uint8_t digits) {
 }
 
 // Preinstantiate
-MarlinSerialUSB customizedSerial1;
-
-#endif // SERIAL_PORT == -1
+#if SERIAL_PORT == -1
+  MarlinSerialUSB customizedSerial1;
+#endif
+#if SERIAL_PORT_2 == -1
+  MarlinSerialUSB customizedSerial2;
+#endif
 
+#endif // HAS_USB_SERIAL
 #endif // ARDUINO_ARCH_SAM
diff --git a/Marlin/src/HAL/DUE/MarlinSerialUSB.h b/Marlin/src/HAL/DUE/MarlinSerialUSB.h
index d8b051d37e01984faf50b294a4ec38e09d364dea..9aece901b12bd1eb596542ac60eea38300706db1 100644
--- a/Marlin/src/HAL/DUE/MarlinSerialUSB.h
+++ b/Marlin/src/HAL/DUE/MarlinSerialUSB.h
@@ -28,7 +28,7 @@
 
 #include "../../inc/MarlinConfig.h"
 
-#if SERIAL_PORT == -1
+#if HAS_USB_SERIAL
 
 #include <WString.h>
 
@@ -88,6 +88,12 @@ private:
   static void printFloat(double, uint8_t);
 };
 
-extern MarlinSerialUSB customizedSerial1;
+#if SERIAL_PORT == -1
+  extern MarlinSerialUSB customizedSerial1;
+#endif
+
+#if SERIAL_PORT_2 == -1
+  extern MarlinSerialUSB customizedSerial2;
+#endif
 
-#endif // SERIAL_PORT == -1
+#endif // HAS_USB_SERIAL
diff --git a/Marlin/src/inc/Conditionals_LCD.h b/Marlin/src/inc/Conditionals_LCD.h
index 2907694fb4c5ff3c3958f3d297404f19b27ff585..dd1f13fae0f8826d786fca9f675d808464d2bec5 100644
--- a/Marlin/src/inc/Conditionals_LCD.h
+++ b/Marlin/src/inc/Conditionals_LCD.h
@@ -683,6 +683,10 @@
   #define SPI_SPEED SPI_FULL_SPEED
 #endif
 
+#if SERIAL_PORT == -1 || SERIAL_PORT_2 == -1
+  #define HAS_USB_SERIAL 1
+#endif
+
 /**
  * This setting is also used by M109 when trying to calculate
  * a ballpark safe margin to prevent wait-forever situation.